TW201130835A - Imidazopyridine derivatives as JAK inhibitors - Google Patents

Abstract

New imidazopyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

Description

201130835 VI. Description of the invention: [Technical field to which the invention pertains] A compound relating to a kind of bite derivative, especially if it is used in the treatment of a secret Kinase; JAK) " improved pathological condition or The disease is screaming. A compound which occupies a derivative or a pharmaceutically acceptable salt listener or N-oxide or stereoisomer. [Prior Art] Cytokines have a key function in regulating many aspects of immunity and inflammation, ranging from development and differentiation of immune cells to suppression of immune responses. Type I and type II cytokine receptors lack the enzymatic activity that mediates signal transduction and therefore need to be associated with tyrosine kinase for this purpose. The JAK family of kinases includes four distinct members, namely JAK1, JAK2, JAK3, and TYK2', which bind to type I and π-type cytokine receptors to control signal transduction (Murray PJ, (20〇7). The JAK- STAT signalling pathway: input and output integration. J Immunol, 178: 2623). JAK kinases are each selective for receptors of certain cytokines. In this regard, 'JAK-deficient cell lines and mice have confirmed the basic role of each JAK protein in receptor signaling: JAK1 is in type II cytokine receptors (IFN and IL-10 family), and their receptors share gpl30 Chains (IL-6 family) and common gamma chains (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21) ( Rodig et al. (1998). Disruption of the JAK1 gene demonstrates Obligatory and nonredundant roles of the Jaks 4 201130835 in cytokine-induced biological response. Cell, 93:373 ; Guschin et al. (1995). A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin -6. Five J. 14: 1421; Briscoe et al.

(1996). Kinase-negative mutants of JAK1 can sustain intereferon-gamma-inducible gene expression but not an antiviral state. V. 15:799); JAK2 in hematopoietic factors (Epo, Tpo, GM-CSF, IL-3, IL_5) and type II IFN (Parganas et al., (1998). JAK2 is essential for signalling through a variety of cytokine receptors. Ce//, 93:385); JAK3 is a receptor for common gamma chain (IL-2) Family (), et al. (1995). Developmental defects of lymphoid cells in JAK3 kinase-deficient mice. /mmwm'O;, 3:771; Thomis et al., (1995). Defects in B lymphocyte maturation and T lymphocyte Activation in mice lacking JAK3. 270:794 ; Russell et al., (1995).

Mutation of JAK3 in a partient with SCID: Essential role of JAK3 in lymphoid development. Sczewce, 270:797); and Tyk2 in the receptors of IL-12, IL-23, IL-13 and type I IFN (Karaghiosoff et al. (2000). Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity, 13:549; Shimoda et al., (2〇00). Tyk2 plays a restricted iole in IFNg signaling, although it is required for IL-12- Medicated T cell function. Immunity, 13:561 ; Minegishi et al., (2006). Human

Tyrosine kinase 2 deficiency reveals its requisite roles in 201130835 multiple cytokine signals involved in innate and acquired immunity. Immunity, 25:745 ) °

Receptor stimulation sequentially leads to jAK activation, receptor filling, STAT protein recruitment, and STAT activation and dimerization caused by acidification. The STAT dimer then functions as a transcription factor to shift to the nucleus and activate transcription of multiple reactive genes. There are seven identified STAT proteins: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

Each specific cytokine receptor preferentially associates with a particular STAT protein. Some associations are independent of cell type (eg, IFNg-STAT1), while other associations may be cell type dependent (Murray PJ, (2007). The JAK-STAT signaling pathway: input and output integration. J Immunol, 178: 2623) ° The phenotype of defective mice has provided insight into the function of each JAK and its cytokine receptor signaling. JAK3 is specifically associated with the common gamma chain of IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 cytokine receptors. Due to this specialized association, JAK3 knockout mice and common gamma chain deficient mice have the same phenotype (Thomis et al., (1995). Defects in Β lymphocyte maturation and T lymphocyte activation in mice lacking JAK3. 270:794; DiSanto et al. People, (1995).

Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. /W/S, 92:377). Furthermore, this phenotype is largely shared with SCID patients who retain mutations/defects in the common gamma chain or JAK3 gene (O'Shea et al., (2004). JAK3 and the pathogenesis of severe combined immunodeficiency. 6 201130835 M9 //mmm〇/, 41: 727). JAK3-deficient mice survive but exhibit abnormal lymphocyte formation, which results in a decrease in thymus size (1/100-1/10 of the wild type). JAK3-deficient peripheral T cells are unresponsive and have an activation/memory cell phenotype (Baird et al., (1998). T cell development and activation in JAK3-deficient mice. J. Leuk. Biol. 63: 669) ° itb and other mice The thymic defect is very similar to that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the absence of IL-7 signaling may indicate that JAK3 -/- mice have this defect (von Freeden-Jeffry et al. (1995). Lymphopenia in Interleukin (IL)-7 Gene-deleted Mice Identifies IL-7 as a non-redundant Cytokine. J Exp Med, 181:1519 ; Peschon et al., (1994). Early lymphocyte expansion is severely impaired in Interleukin 7 receptor-deficient mice. JExp Med, 180: 1955). Similar to SCID humans, these mice have no NK cells, which may be due to the absence of IL-15 signaling (the survival factor of these cells). Unlike SCID patients, JAK3 knockout mice show defective B cell lymphocyte formation, whereas in human patients, B cells are present in the circulation but do not respond, resulting in hypoglobulinemia (O'Shea et al., ( 2004). JAK3 and the pathogenesis of severe combined immunodeficiency. Mol Immunol, 41: 727). The explanation for this is the species-specific difference in the function of IL-7 in mouse and human B and T cell development. On the other hand, Grossman et al. (1999. Dysregulated myelopoiesis in mice lacking JAK3 million/(V) 94:932:939) have shown that loss of JAK3 in the T cell compartment promotes expansion of the myeloid lineage, leading to dysregulated bone marrow formation. . 201130835 JAK2-deficient mice are fatal at embryos due to the absence of directional red blood cell formation. Myeloid progenitors are unable to respond to Ep〇, Tp〇, IL_3 or gm_csf, while G-CSF and IL-6 signaling are unaffected. jAK2 is not required for the production, expansion or functional differentiation of lymphoid progenitor cells (Parganas et al, (1998). JAK2 is essential for signaling through a variety of cytokine receptors. Ce//, 93:385). JAK1-deficient mice die during the perinatal period due to breastfeeding defects. jAK1 specifically binds to the gp130 chain shared by the IL-6 cytokine family (ie, LIF, CNTF, OSM, CT-1) and binds to JAK3 as a common gamma chain receptor by binding to non-consensus receptor subunits. The basic components. In this regard, JAK1-deficient mice showed a hematopoietic defect similar to that of JAK3-deficient mice. In addition, it shows a defect response to neurotrophic factors and all interferons (sputum cytokine receptors) (Rodri et al., (1998). Disruption of the JAK1 gene demonstrates obligatory and non-redundant roles of the JAKs in cytokine- Induced biological response. CW/, 93:373). Finally, Tyk2-deficient mice showed attenuated responses to IL-12 and IL-23 and only partially attenuated the response to IFN-α (Karaghiosoff et al., (2000). Partial impairment of cytokine responses in Tyk2_deficient mice. /wwwmXy,13 : 549 ; Shimoda et al., (2000). Tyk2 plays a restricted role in IFNg signaling, although it is required for IL-12-mediated T cell function. 13:561). However, human Tyk2 deficiency demonstrates that Tyk2 is involved in signaling from IFN-α, IL-6, IL-10, IL-12, and IL-23 201130835 (Minegishi et al., (2006). Human Tyrosine kinase 2 deficiency reveals its requisite Roles in multiple cytokine signals involved in innate and acquired immunity. Immunity, 25:745). 'The role of JAK kinase in transducing signals from numerous cytokines makes it a potential target for the treatment of diseases in which cytokines have a pathogenic effect, such as inflammatory diseases including, but not limited to, allergies and asthma , chronic obstructive pulmonary disease (COPD), psoriasis, autoimmune diseases (such as rheumatoid arthritis, amyotrophic lateral sclerosis, and multiple sclerosis (muitipie) Sclerosis)), uveitis, transplant rejection, and solid and hematological malignancies (such as myeloproliferative disorders, leukemia, and lymphoma). Inhibition of JAK kinases (especially JAK1 and JAK3) produces potent immunosuppression, which is therapeutically useful for preventing transplant rejection. In this regard, the JAK inhibitor CP-690,550 (tasocitinib) has been shown in several animal transplant models by extending the average survival time of the graft (the mouse's heretopic heart transplant, implanted mouse ears) Efficacy of heart allograft, rhesus kidney allograft, rat aorta, and tracheal transplantation (West K (2009)· CP-690,550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid Arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr. Op. Invest. Drugs 10: 201130835 491). In rheumatoid joints, an imbalance between pro-inflammatory and anti-inflammatory cytokine activity promotes induction of autoimmunity, followed by induction of chronic inflammation and tissue destruction. In this regard, the pathogenic role of IL-6 in rheumatoid arthritis (RA) has been clinically confirmed by the use of the anti-IL-6R antibody tocilizumab. IL-6 activates the transcription factor STAT3 via the use of JAK1 binding to the gpl30 receptor chain (Heinrich et al., (2003). Principles of interleukin (IL)-6-type cytokine signaling and its regulation. */. 374: 1) . Constitutive STAT3 mediates abnormal growth and survival properties of RA synovial cells (Ivashkiv and Hu (2003). The JAK/STAT pathway in rheumatoid arthritis: pathogenic or protective? Arth & Rheum. 48:2092). Other cytokines involved in the pathogenesis of arthritis include IL-12 and IL-23, which are involved in the proliferation of Th1 and Th17 cells, respectively; IL-15 and GM-CSF ( Mclnnes and Schett, (2007). Cytokines in the pathogenesis of Rheumatoid arthritis. Nature Rew /mwwwo/· 7:429.). Receptors of these cytokines also use JAK proteins for signal transduction, making JAK inhibitors a potential pleiotropic drug in this pathology. Thus, several JAK inhibitors have been shown to reduce inflammation and tissue destruction in animal models of murine collagen-induced arthritis and rat adjuvant-induced arthritis (Milici et al., (2008). Cartilage By inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. 10: R14). Inflammatosis (inflammatitis bowel disease; 1BD) includes 201130835 two main forms of enteritis: ulcerative colitis and Crohn's disease. Increasing evidence has shown that a variety of cytokines (including interleukins and interferons) are involved in the pathogenesis of IBD (Strober et al., (2002). The immunology of mucosal models of inflammation, and ev Trnmwm?/. 20: 495). It has been shown that activation of the IL-6/STAT3 cascade in TLA cells induces long-term survival of pathogenic sputum cells (Atreya et al., (2000). Blockade of interleukin 6 trans signaling suppresses T-cell Resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn's disease and experimental colitis in vivo. AWwre Med. 6:583). Specifically, STAT3 has been shown to be constitutively active in intestinal tau cells of patients with Crohn's disease and it has been shown that JAK inhibitors block the constitutive activation of STAT3 in these cells (Lovato et al., (2003) Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease. J Biol 278:16777). These observations indicate that the jaK-STAT pathway plays a pathogenic role in IBD and that JAK inhibitors are therapeutic in this environment. Multiple sclerosis is an autoimmune demyelinating disease characterized by the formation of plaques in the white matter. The role of cytokines in the development of multiple sclerosis has long been known. Potential therapies include blocking nTN-gqL-U and IL_23 (Steinman L. (2008). Nuanced roles of cytokines in three major human brain disorders. /m; (4). 118:3557), which is a signal via the JAK-STAT pathway Conducting cytokines. The use of tyrosine 201130835 tyrphostin (JAK inhibitor) has been shown to inhibit IL-12-induced STAT3 phosphorylation and to reduce the incidence of active and passive experimental autoimmune encephalitis (EAE). And severity (Bright et al, (1999) Tyrphostin B42 inhibits IL-12-induced tyrosine phosphorylation and activation of Janus kinase-2 and prevents experimental allergic encephalomyelitis. J Immunol. 162:6255). Another multi-kinase inhibitor, CEP701, has been shown to reduce the secretion of TNF-α, IL-6, and IL-23, as well as to reduce the amount of phosphorylated STATHSTAT3 and STAT5 in peripheral DCs of mice with EAE, thereby significantly improving mice. The clinical course of EAE (Skarica et al, (2009). Signal transduction inhibition of APCs diminishes Thl7 and Thl responses in experimental autoimmune encephalomyelitis. «/. 182:4192·). Psoriasis is a skin inflammatory disease involving the process of permeation and activation of immune cells at the end of epithelial remodeling. The current theory behind the etiology of psoriasis states that there is a cytokine network (Nick〇1〇ffBj. poo?) that controls the interaction between immune and epithelial cells.

Cracking the cytokine code in psoriasis, Nat Med, 13:2420). In this regard, IL-23 produced by dendritic cells was found to increase with IL-12 in psoriatic skin. Il-23 induces the formation of Th17 cells, which in turn produce IL-17 and .IL-22, which is responsible for thickening of the epidermis. IL-23 ^ IL-22 ^ SXAT-3 , in psoriasis skin. Therefore, jAK inhibitors can be therapeutic in this environment. Therefore, it has been found that in the spontaneous cell-dependent mouse model 201130835 of psoriasis, the JAK1/3 inhibitor R348 reduces psoriasis-like skin inflammation (Chang et al., (2009). JAK3 inhibition significant attenuates psoriasiform skin inflammation on CD 18 Mutant PL/J mice. J/mwimo/. 183:2183 ).

Diseases caused by Th2 cytokines, such as allergies and asthma, can also be targets for JAK inhibitors. IL-4 promotes Th2 differentiation, regulates B cell function and immunoglobulin class switching, regulates eotaxin production, induces IgE receptors and MHC II expression on B cells, and stimulates mast cells. Other Th2 cytokines such as IL-5 and IL-13 may also contribute to the recruitment of eosinophils by stimulating eosinophil chemokine production during bronchoalveolar lavage. Pharmacological inhibition of JAK has been shown to reduce the expression of IgE receptors and MHC II induced by IL-4 stimulation on B cells (Kudlacz et al., (2008). The JAK3 inhibitor CP-690, 550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia. Zwra/jeim J. 582: 154). In addition, JAK3-deficient mice exhibited weak eosinophil recruitment and mucus secretion into the trachea after 〇VA challenge compared with wild-type mice (Malaviya et al., (2000). Treatment of allergic asthma by targeting Janus kinase 3-dependent leukotriene synthesis in mast cells with 4-(3*, 5*- dibromo-4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P97). J7^T 295:912.). In this regard, systemic administration of CP-690, 550 JAK inhibitors in mice has been shown to reduce eosinophil counts in BAL and reduce leukotriene chemokines in a murine model of eosinophilia in the lungs. Content with IL13 (Kudlacz et al, (2008). The JAK3 inhibitor CP-690, 550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia. V. (10) Opeaw J. p/zflTvw. 582: 154). There is growing evidence that cytokines play a causative role in ocular inflammatory diseases such as uveitis or dry eye syndrome. Some cytokines (such as IL-2, IL-6, IL-12, and IFNg) associated with experimental autoimmune uveitis will be affected by JAK inhibition (Vallochi et al., (2007). The role of cytokines in the Regulation of ocular autoimmune inflammation. CyioA: GVowi/z Faciors and ev. 18:135). In this regard, drugs or biological products that interfere with IL-2 signaling, such as cyclosporine or anti-IL-2 receptor antibodies (daclizumab), have been shown to be associated with keratoconjunctivitis sicca and Efficacy in the treatment of refractory uveitis (Lim et al, (2006). Biologic therapies for inflammatory eye disease. Clin Exp 〇pht 34: 365). Similarly 'allergic conjunctivitis (a common allergic eye disease characterized by conjunctiva Hyperemia, mast cell activation, and eosinophil infiltration can benefit from JAK inhibition. STAT6-deficient mice that show a TH2-mediated immune response (which is usually primed by IL-4) do not produce typical early and late responses, suggesting JAK inhibition cancels the IL-4 pathway and is therapeutic in this environment (Ozaki et al., (2005). The control of auergic conjunctivitis by suppression of cytokine signaling (S〇CS) 3 and SOCS5 in a murine model. J/wmwwi ?/, 175:5489). There is growing evidence that STAT3 activity is involved in tumor formation in the process of 201130835 (eg, cell cycle disorders, promotion of uncontrolled A key role in growth, induction of survival factors, and inhibition of apoptosis (Siddiquee et al., (2008). STAT3 as a target for inducing apoptosis in solid and haematologicaltumors. CW/ and .18: 254). Dominant-negative mutants or antisense oligonucleotides antagonize STAT3 to promote cancer cell apoptosis, angiogenesis inhibition, and up-regulation of host immunity. The inhibition of constitutively active STAT3 in human tumors by means of jAK inhibitors provides treatment for this. Therapeutic options for disease. In this regard, the use of the JAK inhibitor glycosyl phosphorylation inhibitor has been shown to induce malignant cell apoptosis and inhibit cell proliferation in vitro and in vivo (Meydan et al., (1996). Inhibition of Acute lymphoblastic leukemia by a JAK-2 inhibitor. Nature, 379:645). The JAK-STAT pathway disorders of eutrophic malignancies can benefit from jAK inhibition. Recent studies have suggested a range of myeloproliferative diseases (IhIe and

Gililand, 2007) (including chromosomal translocations and mutations in the pseudo-kinase domain in p〇iyCythemia vera, myelofibrosis, and essential thrombocythemia) Such as the JAK2V617F mutation) dysregulates JAK2 kinase activity. In this regard, several kinds of jak inhibitors that effectively treat jAK2 have been proposed, such as TG-101209 (Pardanani et al., (2007). TG101209, a small molecular JAKft2-selective inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations Leukemia. 21:1658 - 68 ) ' TG101348 (Wernig et al., (2008). Efficacy of TG101348, a 15 201130835 selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell, 13: 311 ) , CEP701 (Hexner et al., (2008). Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood, 111: 5663 ) ' CP-690,550 (Manshouri Et al., (2008). The JAK kinase inhibitor CP-690, 550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation. Cimcer <Scz·, 99: 1265) and CYT387 (Pardanani et al., (2009). CYT387, a selective JAK1/JAK2 inhibitor: invitro a Sssment of kinase selectivity and preciinical studies using cell lines and primary cells from polycythemia vera patients. 23:1441) is used to treat myeloproliferative diseases based on its antiproliferative activity against cells bearing the JAK2V617F mutation. Similarly, sputum cell leukemia caused by the transformation of human sputum leukemia virus (HTLV-1) is associated with constitutive activation of JAK3 and STAT5 (Migone et al., (1995). Constitutively activated JAK-STAT pathway in T cells transformed wit; HTLV-I. 269: 79) and JAK inhibitors are therapeutic in this environment (Tomita et al., (2006). Inhibition of constitutively active JAK-STAT pathway suppresses cell growth of human T-cell leukemia virus type I- Infected T cell lines and primary adult T-cell leukemia cells. Retrovirology, 3:22). JAK1 activating mutations have also been identified in adult acute lymphoblastic 201130835 maternal cell leukemia caused by T cells (Flex et al., (2〇〇8) such as melon station & taken JAK1 mutations in adult acute lymphoblastic leukemm. J. and φ. mm. 205:751_8), indicating that this kinase can be used as a benchmark for the development of novel anti-leukemia drugs. It is expected that the dry JAK kinase or JAK kinase (especially JAKI, jAK2 and JAK3 kinase) is therapeutically suitable for the treatment or prevention of diseases including neoplastic diseases (such as leukemia, lymphoma, solid tumors); Transplant rejection, bone marrow transplantation (eg graft versus host disease); autoimmune diseases (eg diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease); respiratory inflammatory diseases (eg asthma, chronic obstruction) Pulmonary disease), inflammation-related eye disease or allergic eye disease (eg dry eye, glaucoma, uveitis, diabetic retin〇pathy, allergic conjunctivitis or age-related macular degeneration (age_rdated dirty gold degeneration)) and skin Inflammatory (such as atopic dermatitis or psoriasis).

It is expected that many conditions benefit from novel compounds that are involved in the modulation of the JAK pathway or JAK kinase 'immediately obvious' regulatory pathways and the use of such compounds should provide substantial therapeutic benefit to a variety of patients. Provided herein are novel imidazopyridine compounds for use in the treatment of a JAK pathway or inhibition; AK kinases are therapeutically useful conditions. The compounds of the present invention are simultaneously effective; VIII], JAK2, and JAK3 inhibitors, i.e., pan-JAK inhibitors. This property makes it suitable for the treatment or prevention of pathological conditions or diseases, such as myeloproliferative disorders (such as true plethora, thrombocytosis or myelofibrosis), leukemia, lymphoma and solid tumors. Bone marrow and organ transplant rejection; or immune-mediated diseases such as autoimmune and inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (such as ulcerative colitis or Crohn Disease, inflammation-related eye disease or allergic eye disease (such as dry eye, uveitis or allergic conjunctivitis), allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), and skin inflammatory diseases (such as atopic dermatitis) Or psoriasis). Certain imidazopyridine derivatives have been found to be novel and potent JAK inhibitors and are therefore useful in the treatment or prevention of such diseases. SUMMARY OF THE INVENTION Accordingly, the present invention relates to a compound which is an imidazopyridine derivative of the formula (I), or a pharmaceutically acceptable salt or solvate thereof or an N-oxide or a stereoisomer thereof, which is used. For the treatment of pathological conditions or diseases that are easily ameliorated by inhibition of Jars Kinase (JAK):

201130835 Formula (I) wherein m is deuterium or an integer from 1 to 3; Z is an oxygen atom or a group NR5; wherein X is independently represented by X and Y, and at least one of a -CR9 group and Y is represented by Nitrogen atom

Rl, 尺2, Κ·3, R4 and R9 each independently represent a atom; cyano; straight or branched chain crc6 alkyl; oxygen f.; halogen ^ beautiful crC4 secret; Cl_Q weiji; < iCrQ alkyl)(C3_C7), a monocyclic or polycyclic c5-c14 radical containing at least one 5- to 14-membered heteroaryl selected from the group consisting of 0, S, and 1^. X < heteroatoms, containing a 5- to 14-membered heterocyclic group selected from the group consisting of a hetero atom of fluorene, S, and N; a bicyclic group containing a monocyclic C5_C9 aryl face aryl group directly bonded to a 5- to 9-membered cycloalkyl group or a heterocyclic group; The heteroaryl or heterocyclic group contains at least one hetero atom selected from the group consisting of ruthenium, S and N; an azabicycloalkyl group having up to 12 carbon atoms or an aza-bicycloalkenyl group having up to 12 carbon atoms, Wherein the dilute group, alkynyl group, halomorphyl group, alkyl group, cycloalkyl group, cycloaliphatic group, aryl group, heteroaryl group, heterocyclic group, bicyclo group, aza-bicycloalkyl group and aza-bicyclic ring The alkenyl group is unsubstituted or substituted with one or more substituents selected from the substituents Ra, and the alkyl group is unsubstituted or substituted with one or more substituents selected from Rb; or Ri, R2, R3, R4 and r9 independent _SR13 group, -SOR13 201130835 group, -S(0)2R13 group, _S(0)2NRi3Ri4 group, -NRI3S(0)2R14 group, -NR13S(0)2NR14 group, -0R13 a group, a _c(0)0Ri3 group, a -0-C(0)R13 group, a -C(〇)-(CH2)n-R13 group, a _NR13R14 group, -C(0)-(CH2) n-NR丨3R 4 group, -NR13C(〇)-(CH2)n-R14 group or -NR13C(0)-(CH2)n-NR 丨4R15 group, wherein each η is 〇, ι or 2; or in the presence of two adjacent -CR9 groups, two adjacent _Cr9 groups and their bonded carbon atoms optionally form a c5_Ci2 aryl or a 4 to 12 membered heteroaryl, naphthenic Or a heterocyclic group, said heteroaryl group and heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S and N, said aryl group, heteroaryl group, cycloalkyl group and heterocyclic group being unsubstituted or via One or more selected from the group consisting of a halogen atom, a linear or branched chain CrC6 alkyl group, a monocyclic or polycyclic c5_c14 aryl group, a 5- to 14-membered heteroaryl group containing at least one hetero atom selected from the group consisting of hydrazine, S and N, or Substituent substitution of a 5- to 14-membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S and N, wherein the alkyl group An aryl group, said heteroaryl group, and said heterocyclic group substituent are unsubstituted or one or more selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a linear or branched chain Ci_C6 alkyl group, or a Ci_c4 halogen group Substituent substitution;

Rs represents a hydrogen atom, a linear or branched chain CrC6 alkyl group, and the alkyl group optionally has one or more selected from the group consisting of a hydroxyl group, a cyano group, a crc4 alkyl group, a crc4 hydroxyalkyl group, a CrClG cycloalkyl group, a phenyl group. Or a 6-membered substituent substituted with a N-heterocyclic ring-substituted ' or R5 represents a _S(〇)2R10 group, a -S(G)2NR10Rn group, a -C(0)〇R1〇 group, _c(〇) )_(CH2)n_Ri. a group or a -C(0HCH2)n-NR1〇Rll group; R6 and R7 each independently represent a hydrogen atom, or a straight chain or a branched chain 20 201130835 cvc6 alkyl group 'the silk-like test-- or a plurality selected from (4) 丨C4 haloalkyl, crC4 hydroxyalkyl, Ci_c4 alkoxy broad-based, C3-C7 cycloalkyl, stupid into 6-membered 4-alkoxythiol;

Rs represents a hydrogen atom; a halogen atom; a cyanoalkyl group; a sinter group; a C2_C4'5 branched CA group; an IQ wire)-(CrC4 alkoxy group); a 5 to 14 (10) ring group of a nitrogen group; Or 3 芳美Ϊ ^ Ϊ silk feeding; a C5_C9 aryl or a heterocyclic group of 5 to 9 membered ring or heterocyclic group, and having at least one hetero atom selected from o, s, and ν; Atom aza-azityl or having up to 12 carbons of a ruthenium, an alkynyl group, a (tetra) group, a pyrenyl group, a cycloalkyl group, a cyclohetero group, a heterofluorenyl group, a heterocyclic group, a heterocycloalkyl ketone, a bicyclic group, a nitrogen from an Ra-alkyl group, and an aza-bicycloalkenyl group unsubstituted or via one or more selected groups a, ((^1<:4 alkyl)-CN group Or -(CrC4 alkyl)-C(0)NR,R,,substituent substituted with a substituent wherein 'R and R" are the same or different and are selected from the group consisting of hydrogen and a straight or branched chain CrC4 alkyl group; And the alkyl group is unsubstituted or substituted with a substituent selected from Rb; or the rule 8 represents a -SR13 group, a -SOR13 group, a -s(o)2r13 group, a 2NruR14 group, _NRl3S (〇) 2Ri4 group, _NRl3s(0)2NRi4 21 201130835 group, -ORu group, -C(0)0R13 group, _〇_c(〇)Ri-C (9)-(CH2)n-Rl3 group, 13R14 group ^1 -c (〇hch2vnr13r14 base®, marriage 13C(Q)_( CH2) -NR13C(0HCH2)n-NR14R15 group, wherein n is 〇, 1 or f, group or Rs together with Rs and the nitrogen atom to which the bond is bonded, H) a saturated heterocyclic group containing one or The two nitrogen atoms are as a linear or branched chain CrQ alkyl group, and the monocyclic or polycyclic C5_Cb 乂 has at least one hetero atom selected from 0, S and N, 5 to 14 bis' 3, and contains at least one selected from the group consisting of ruthenium, S and N's Miscellaneous Eyebrows', Fangtu, Mei, Paste I «5 to 14 heterocyclic groups of the hetero atom of the π-SOR10 group...c(〇)_(CH2)n_Ri〇 group or •CXOHCEbVNRu^ a group substituted wherein each of the alkyl group, the aryl group, the heteroaryl group, and the heterocyclic group is unsubstituted or has one or more selected from the group consisting of a functional atom, a trans group, a cyano group, and a linear chain. Or a branching bond, or a substituent of CVC4_silk, and substituted or substituted with or a plurality of substituents selected from a halogen atom, a trans group, a cyano group or a haloalkyl group; When m is 〇, r8 * is a ·SRi3 group, _s〇Ri3 group -S(0)2R13 group Group, _s(〇)2NR13R14 group, Νυ(〇)2ΐ1ι4 group NR13S(0)2NR14 group, _〇r13 group, ·〇·^(〇)Κΐ3 group, -NRURM group, _NRnC(9)_( CH2)n_Ri4 group or -·13<3(0)-((:Η2)η-ΝΚ_]4Κ15 group, ν

Where V

Ra is a time atom; secret; honest; linear or branched chain ^6 炫基' said silk unsubstituted or by - or more pure silk generation; Ci_C4 South burning 22 201130835 base; CVC4 hydroxyalkyl; CrC: 7 ring An alkyl group or (^-(:7 cycloalkenyl group; a monocyclic or polycyclic CVCM aryl group which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; contains at least one a 5- to oxime heteroaryl group selected from the group consisting of a hetero atom of hydrazine, S, and N, which is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group; 5 to 14 membered heterocyclic groups of the hetero atom of hydrazine, S and hydrazine; _SRi 〇 group; -SOR10 group; -S(〇) 2R10 group; -S(〇)2NR10RU group; • nri〇s (〇) 2Rii group; -NRioSiPLNRu group; _〇R1 〇 group; -C(O)OR10 group; _C(O)_CH2-〇R10 group; -C(0)-(CH2)n- 〇-(CH2)pRi〇 group; -C(〇HCH2)n_〇-(CH2)p〇-R10 group; -〇-C(〇)R10 group; -C(O)-(CH2) n-R10 group, -NR^oR^ group; -QOMCHA-NRwRu group; -R10C(〇HCH2)n-NRnR12 group;_C(CrC4 alkyl)2-C(O)-(CH2)n -NR10Rn a group ^ - NRwQOHcmR" group or group ' wherein each η is 〇 or an integer from 1 to 5' and wherein p is an integer from 1 to 3;

Rb is cyano; hydroxy; straight or branched chain crC6-based; CrC#-based; crQ via alkyl; cvc: 7-cycloalkyl or eve? ring-like; mono- or polycyclic CVCh aryl The aryl group is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; and a 5- to 14-membered heteroaryl group containing at least one hetero atom selected from the group consisting of hydrazine, s and N, the heteroaryl group Substituent unsubstituted or substituted by one or more substituents selected from a functional atom or a cyano group; 5 to η heterocyclic 1 containing at least one hetero atom selected from the group consisting of hydrazine, S and N; 23 201130835

-SR10 group; -SOR10 group; _s(O)2R10 group; -S(0)2NR1()Rii group; -NRwSCC^Rh group; -NRioSCOhNRu group; 〇Ri〇 group; C(O)OR10 group; _C(0)_CH2-ORl〇 group; -C(O)-(CH2)nO-(CH2)pR10 group I -CX〇)-(CH2)nO-(CH2) p〇-R10 group; _0_C(0)Ri〇 group; -C(O)-(CH2)n-R10 group; -NR^Rn group; -C(O)-(CH2)n-NR10Rn a group; _Ri〇c(〇)_(CH2)n_NRiiRi2 group; _c(crc4 alkyl)2_c(0)_(CH2)n_NRi〇Ru group has a -NR^OKCHU group or _NRi〇c ( 〇)_(CH2)n_NRiiRu group, wherein each η is an integer of 0 or 1 to 5, and wherein 0] to: an integer; &

Rig, Ru and R!2 each independently represent a hydrogen atom, a cyano group, or a branched chain crc6 alkyl group, a crc4 6 yard group, a CrC6 group, a c alkoxy group, a c3-c7 ring group, a stupid group, -(CrC4 via 乂4, -(phenyl), containing 5 to 6 members of the mono-heteroaryl group selected from the f-subunits, containing 2 or 3 selected moons 1 original: 5 to 6 members of the hetero atom a cyclic group containing 1, 2 or 3 nitrogen/C7 heterocyclic fluorenyl groups, containing a monocyclic C5_C6 aryl group or a heteroaryl A straight group, which is a 5 to a bicyclic group having a cyclofilament or a heterocyclic group, , 2 or 3 heteroatoms selected from the group consisting of oxygen and nitrogen atoms ί ϊΐ ί:: oxime, cycloalkyl, stupid, oxime-substituted, heterocyclic ketone, and bicyclic Substituted or one or more selected from substituted diradicals (3)^^^ 24 201130835

Rc is a halogen atom, a hydroxy group, a cyano group, a linear or branched chain heart-alkyl group, a CVQ dentate group, a crc4 alkoxy group, a crc4 alkyl group, a C3-C7 cycloalkyl 'phenyl group, containing 1, 2 Or 5 to 6 membered monocyclic heteroaryl groups of 3 nitrogen atoms, 5 to 6 membered heterocyclic groups containing 1, 2 or 3 nitrogen atoms, or c3-C7 heterocyclic rings having 1, 2 or 3 nitrogen atoms Alkyl ketone 'the phenyl group is unsubstituted or substituted with one or more dentate atoms, and the heteroaryl, heterocyclic, and heterocyclic ketone ketone groups are unsubstituted or one or more straight Chain or branched chain Crc3 alkyl substitution;

Rd is cyano 'CrC4 dentate alkyl, CrC4 alkoxy, CrC4 hydroxyalkyl 'Q3-C7 cycloalkyl' phenyl, 5 to 6 membered monocyclic hydroxy group containing hydrazine, 2 or 3 nitrogen atoms, a 5- to oxime heterocyclic group containing 1 to 2 or 3 gas atoms, or a c3_C7 heterocycloalkyl ketone group having 1, 2 or 3 nitrogen atoms, which is unsubstituted or one or more a aryl atom, and the heteroaryl, heterocyclic, and heterocycloalkyl ketone groups are unsubstituted or substituted with one or more straight or branched chain CrC3 groups;

Ru, Rl4 and each independently represent an argon atom, a cyano group, a linear or knife-chain branched CrC6 alkyl 'crc4-alkyl group, a C丨·c4 hydroxyalkyl group, a _(CrC, yl)-(CrC4 alkoxy group) a 9- to 5-membered heterocyclic group containing at least one hetero atom selected from the group consisting of s and N, a C!-C4 alkoxy group, a monocyclic or polycyclic C5_Cl4 aryl group, containing at least one

And a 5 to 14-membered heteroaryl group of a hetero atom of N, or a 5- to 14-membered heterocyclic group containing at least one hetero atom derived from a sulfonium, q IV XI basin, a hydroxyalkyl group, an oxime group, an aryl group, and a heterocyclic group which are unsubstituted, an oxygen group, a sulfhydryl group, a heterocyclic group or substituted with one or more substituents selected from the substituents Ra 25 201130835, and the alkane The base-view case is substituted with one or more substituents selected from Rb. The present invention further provides a novel imidazopyridine derivative of the formula (I), or a pharmaceutically acceptable salt or solvate thereof or an N-oxide or a stereoisomer or a deuterated derivative, wherein m, X, γ, ζ and heart to heart are as defined above. The conditions are as follows when X represents a nitrogen atom, X represents a -C R9 group, and Re represents a 5- to 6-membered heterocyclic group containing a nitrogen atom, said nitrogen The atom is not bonded to the _z_(CR6R7)m• moiety, and the derivative is not substituted for the substituent of the second butoxycarbonyl or benzyloxycarbonyl group. The synthetic methods and intermediates described above are suitable for the preparation of the compounds. A pharmaceutical composition is also provided which comprises a compound of the invention and a pharmaceutically acceptable transfer or carrier. Series = two inhibition of Janus _ (; α κ) to improve the disease and solid tumors; bone _ and 2, leukemia, lymph dysfunction = = = disease 'such as spinal transmission disease, white blood reaction and age-free He. And (4) transplant rejection disease, chronic gastroenterology: plug = (COPD), atopic skin: nasal =, sexual disease =, ': =;" can be used to treat the sacral hyperplasia of the disease and solid tumor In this aspect 26 201130835, the treatment is usually achieved by inhibiting the Gener of the individual, and the compound of formula (I) can be used to treat bone. In rejection; immune-mediated disease and inflammatory Disease M and organ transplantation and organ transplant rejection; and immune-mediated diseases such as bone marrow and organ transplant rejection. Disease, such as bone marrow. The invention also provides a pyridine derivative as defined herein, or a medicament thereof Achially acceptable) imidazopyrene or stereoisomeric t-derivatives, wherein: ^ = 1 仏 oxidation, in detail, the present invention provides a species such as Naskin kinase, a bite derivative, or It is pharmaceutically acceptable to digest and translocate or stereoisomers or deuterated derivatives, which are used in either N-enzymes or the like. A method for improving pathological conditions or diseases, details = (JAK) The pathology or disease is selected from the group consisting of a spinal proliferative disorder, a diseased disease, and a solid tumor; bone marrow and a white matter = 2 lymphoid-mediated diseases and inflammatory diseases, immune diseases, lymph Malignant diseases and entities _; bone = = white: 2; and immune-mediated diseases 'more two = = disease or sarcoma, multiple asthma, slow sister New Zealand kiss Y Cai, recorded rhinitis, phlegm; The method comprises administering to a subject having atopic dermatitis and a cowhide a therapeutically effective amount of a pharmaceutical composition comprising or a compound or a diluent or carrier as hereinbefore described. In particular, H inhibits the individual's Genus kinase to achieve a Genus kinase that inhibits an individual in need thereof. The individual is administered to the individual in need of the treatment. A compound as defined herein or a pharmaceutical composition comprising a pharmaceutically acceptable diluent or a pharmaceutical composition as defined herein. A combination product comprising: (1) a composition as herein; and (ii) - other active substances, Known to apply = Taiwanese treatment of spinal proliferative disorders (such as true plethora, primary blood II.:. or bone _ vitamin), leukemia, lymphoid malignant disease and real-time private il bone marrow and 11 official transplant rejection Reaction; immune-mediated disease with a inflammatory disease such as spinal proliferative disorder, platinum disease, lymphoid malignancy, disease, and physical axis LXA|i officially repellent response; and disease-free 'more specifically' Pathological conditions or diseases, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (such as / cancerous colitis or Crohn's disease), dry eye, (four) membranous inflammation, allergic conjunctivitis, Allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, and psoriasis. As used herein, the term crc6 alkyl includes the optionally substituted straight or branched chain group, which has 6 carbon atoms, preferably 4 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, t-butyl, n-pentyl, methyl butyl, 2 methyl 28 201130835 butyl, different Pentyl, 1-ethylpropyl, 1,1-dihydroxypropyl, 1,2,dipropyl, n-hexyl, 1-ethylbutyl, 2-ethylbutyl-1,1-di Methyl butyl, 1,2-dimethylbutyl, 1,3-dimercaptobutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 2-methylpentyl Base, 3-methylpentyl and isohexyl. The term Cs-C4 alkenyl, as used herein, encompasses optionally substituted straight or branched chain mono- or polyunsaturated groups having from 2 to 4 carbon atoms. Examples include vinyl, allyl, 1-propenyl, isopropenyl, butenyl, 2-butenyl and 3-butylenyl. The term CVQ alkynyl, as used herein, encompasses optionally substituted straight or branched chain mono- or polyunsaturated groups having from 2 to 4 carbon atoms. Examples include 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl and 3-butynyl. When it is mentioned that an alkyl, alkenyl or alkynyl group may be optionally substituted, it is intended to include a straight or branched alkyl, alkenyl or alkynyl group as defined above, which may be unsubstituted or at any position — or a plurality of substituents (for example, via i, 2 or 3 substituents). When two or more substituents are present, each substituent may be the same or different. The optionally substituted alkenyl group is usually unsubstituted or substituted with W or 3^ which may be the same or different substituents. Preferred substituents on the substituent of the alkenyl group are «atoms and light groups, and more preferably halogen atoms. The optionally substituted block groups are typically not substituted with the same or different substituents of r. The m on the block base is unsubstituted. The substituent on the lysine is a self-priming atom ii 29 201130835, and more preferably a dentate atom. The term Ci_c4 haloalkyl, as used herein, is an alkyl group bonded to one or more, preferably 1, 2 or 3, halogen atoms, for example, or an alkyl group. The dentate base is preferably selected from the group consisting of _CC13 and -CF3. The term CrC6 hydroxyalkyl as used herein encompasses a straight or branched alkyl group having from 丨 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein one or more carbon atoms are passed through one or more, Preferably i or 2, more preferably i hydroxy substituted. Examples of such groups include hydroxymethyl, hydroxyethyl, hydroxypropyl and hydroxybutyl groups. As used herein, the term crc:4 alkoxy includes, as appropriate, a straight or branched chain oxygen-containing group, each having a enthalpy of 丨 to 4 carbon atoms. The alkoxy groups are usually unsubstituted or substituted by 1, 2 or 3 substituents which may be the same or different. Substituents on alkoxy groups are generally not themselves substituted. Preferred alkoxy groups include a decyloxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, a second butoxy group, a third butoxy group, a trifluoromethoxy group, and a difluoromethyl group. Oxyl, hydroxydecyloxy, 2-hydroxyethoxy and 2-hydroxypropyloxy. Soil As used herein, a CrQ alkoxycarbonyl group is typically the CrC4 alkoxy group bonded to a carbonyl group. 〇, 土 As used herein, the term (: 3_(:10 cycloalkyl) encompasses a saturated monocyclic or polycyclic carbocyclic group having 3 to 1 carbon atoms, preferably 3 to 7 carbon atoms. C 3 - C1 〇cycloalkyl is usually unsubstituted or substituted with hydrazine, 2 or 3 substituents which may be the same or not. When the CrCi fluorene ring has 2 or more substituents, the substituent may be The same or different. The substitution on the C3_C10 ring courtyard base 201130835 The base 4 itself is unsubstituted. The polycyclic loop filament contains two or more slightly ring filaments, preferably two loop filaments. The polycyclic Wei group is usually selected from X-free Cai Ji, ^ ring [2.2.2] octyl, adamantyl, camphoryl or borneol. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclodecyl, cyclohexyl, cycloheptane Base, cyclooctyl, cyclodecyl and cyclodecyl. As used herein, the term C3-Cu)cycloalkenyl encompasses partially unsaturated carbon having from 3 to 10 carbon atoms, preferably from 3 to 7 carbon atoms. The cyclic alkenyl group is generally unsubstituted or substituted by hydrazine, 2 or 3 groups which may be the same or different. The C3_ClG ring has 2 or more substitutions. The substituents may be the same or different. The substituents on the ring-dense group are usually unsubstituted by themselves. Examples include a ring T-alkenyl group, a ring-contact group, a cyclohexyl group of cyclohexyl, a ring-reading red ring, and a ring oxime. As used herein, the term c5_Ci4 aryl, t6, more preferably CVC1Q monocyclic indole ring aryl, such as phenyl = phenyl is preferred. The substituted or substituted 1, 2 or The three substituents which may be the same or different may be the same or the same. Unless the substituent is used, the substituent on the base is usually unsubstituted by itself. The shell I CVCu is fragrant to two == to 14 members of the heteroaryl group. Betty, preferably 5 to 10 member ring system, more preferably 5 to 6 members, including at least one heteroaromatic ring and N hetero atom. 5 to 14 members of the second or second == 201130835 The fused ring 'at least one of the rings contains a hetero atom. The visually substituted 5 illusion 4 2 ^ ^ ^ ^ member base with 2 or more takes 7 = 4 = body = regulation, 5... = Γ1: ί and iron, prepared, two bite base, 嗓-based '' 吼疋 、, benzo fluorenyl, aryl, argyl, sulfhydryl, quinolinyl, phenyl, pyridazin, _ base, 啥鸠(4) Base, recorded '^Qinji', _ base, different, Duo Lin Tu, Gossip D wood base, oxazolidinyl, acridinyl, sulfhydryl, π-bisazolyl, _ 対 [ [3, 4-d] Qianji, 1Η_„ than 嗤[3,4_d] squirting, squeaking [2,3-d] squeaking base and a variety of sputum and biting bases — as used herein, the term The 5- to 14-membered heterocyclic group generally encompasses a non-aromatic saturated or unsaturated CrCH carbocyclic ring system, preferably a c5_Cl〇 carbocyclic ring system, more preferably one or more of the VC:6 carbocyclic ring systems (eg, 1, 2, 3 or 4 carbon atoms, preferably 1 or 2 carbon atoms are replaced by a hetero atom selected from N, hydrazine and s. The heterocyclic group may be a single ring or two or more fused rings, at least one of which contains a hetero atom. When a 5- to 14-membered heterocyclic group has 2 or more substituents, the substituents may be the same or different. The optionally substituted 5 to 14 membered heterocyclic group is usually unsubstituted or substituted with 1, 2 or 3 substituents which may be the same or different. 5 to 14 members 32 201130835 Substituents on heterocyclic groups are generally unsubstituted by themselves. Examples of the 5- to 14-membered heterocyclic group include a stimulating group, an n-biting group, a specific ratio, a piazinyl group, a morphinyl group, a thio-allinyl group, an η-mercapto group, and a π-pyrene group. Lysine, piraz〇lidinyl, 〇6 pyridine, triazolyl, pyrazolyl, benzyl, imidazolidinyl, imidazolyl, oxonium 8 , 4,5-dihydrooxazolyl , I benzofuran-1 (3H)-ketone, 1,3-dioxol-2-one and 3-aza-four-wind D-flanyl. When the 5- to 14-membered heterocyclic group has 2 or more substituents, the substituents may be the same or different. As used herein, the term 6-membered saturated heterocyclic group is a saturated carbocyclic ring system in which one carbon atom is replaced by N and, as the case may be, 1 or 3, preferably 1 or 2 other carbon atoms. It is selected from the substitution of N and oxime. The 6-membered saturated N-containing heterocyclic group is usually unsubstituted or substituted with hydrazine, 2 or 1 substituents which may be the same or different. Unless otherwise specified, the substituents on the 6-membered saturated N-containing heterocyclic group are themselves unsubstituted. Examples of 6-membered saturated N-containing heterocyclic groups include piperidinyl and piperazinyl. As used herein, the term CrC7 heterocycloalkyl ketone group generally encompasses a non-aromatic saturated or unsaturated CrC7 carbocyclic ring system in which one carbon atom is replaced by a C== fluorene group and is 2 or 3, preferably 1 Or two, more preferably one, other carbon atoms are preferably replaced by N. Examples include pyridone and pyrrolidone groups. As used herein, aza-bicycloalkyl having a spectrum of up to 12 carbon atoms represents a fused ring system formed from a cycloalkyl group as defined herein and an N-containing heterocyclic group 33 201130835. As used herein, the term and bicycloalkenyl embraces aza-bicycloalkyl as defined herein, aza-bond of a slave atom. 3 An unsaturated carbon-carbon as used herein, containing a single bond to a 5 to 9 membered cycloalkyl group. The aryl group or the heteroaryl group is a single bond. As used herein, a gas heterogeneous group and a 10 alkyl group are used. Some of the original ΐ原团, which existed in the general structure of this ming, are replaced by circumstances. This means that this @m 77, chain and ring may be unsubstituted or substituted at any position by multiple (eg 1, 2, 3 or 4) substituents, thereby forming a second;:, group, moiety, chain And the hydrogen atoms of the ring are replaced by: a group, a sub, a group, a moiety, a chain, and a ring. When the above substituents are present, the respective substituents may be the same or different. The substituents returned are usually unsubstituted by themselves. Typically, when a cyclic group is bridged by a stretch or a dialkyl group, the bridged alkyl group is bonded to the ring at a non-adjacent atom. As used herein, the term halogen atom encompasses chlorine, gas, moisture, and = atom. The halogen face is usually fluorine, chlorine or _, preferably a chlorine wheel. The technique #函基 has the meaning of Xiangtong when used as the first word. - As used herein, the term pharmaceutically acceptable salt comprises a salt formed with a medically acceptable acid or test. Pharmaceutically acceptable acids include inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, diphosphoric acid, hydrobromic acid, hydrogen 34 201130835 iodic acid and nitric acid; and organic acids such as citric acid, fumaric acid, butylene Diacid, malic acid, mandelic acid, ascorbic acid, oxalic acid, succinic acid, tartaric acid, benzoic acid, acetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or p-butanesulfonic acid. The pharmaceutically acceptable base comprises an alkali metal (e.g., sodium or potassium) and an alkaline earth metal (e.g., calcium or magnesium) hydroxide; and an organic base such as an alkylamine, an aralkylamine, and a heterocyclic amine. Other preferred salts of the invention are quaternary ammonium compounds wherein the anthracene equivalent anion (X-) is associated with a positive charge of the N atom. Χ_ can be an anion of various inorganic acids, such as gas ions, bromide ions, iodide ions, sulfates, nitrates, phosphates; or anions of organic acids, such as acetate, maleate, fumarate , citrate, oxalate, succinate, tartrate, malate, mandelate, trifluoroacetate, mesylate and p-toluene. X- is preferably an anion selected from the group consisting of chloride, bromine, iodide, sulfate, nitrate, acetate, maleate, oxalate, succinate or trifluoroacetate. X- is more preferably a gas ion, a bromide ion, a trifluoroacetate or a methanesulfonate. As used herein, an N-oxide is formed from a tertiary amine or imine present in a molecule using a conventional oxidizing agent. Usually 'in the compound of formula (I): R1, R2, 3, R4 and r9 each independently represent a hydrogen atom, a halogen atom; a nitrogen group; a linear or branched Crc6 alkyl group; a C2-C4 alkenyl group; C4v = group; CK: 4 i alkyl; Ci_c4 alkyl; C3_Ci〇 cycloalkyl; C3_Ci anthracene; monocyclic anthracene CVC14; containing at least one heteroatom selected from 0, S and N 5 to 14 membered heteroaryl; containing at least one selected from 35 201130835

a 5- to 14-membered heterocyclic group of a hetero atom of j μ and N; a bicyclic group containing a monocyclic c5_c9 group or a heteroaryl group directly bonded to a 5- to 9-membered cycloalkyl or heterocyclic group, said heteroaryl Or a heterocyclic group containing at least one atom selected from the group consisting of ruthenium, s, and N; a nitrogen having up to 12 carbon atoms, a diguanyl group or an aza-bicycloalkenyl group having up to 12 carbon atoms, wherein Alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, bicyclo, aza-bicycloalkyl, and aza-bicycloalkenyl Substituted or substituted with one or more substituents selected from the substituents Ra, and the alkyl group is unsubstituted or substituted with one or more substituents selected from the group; or Ri, R2, R_3, R4 and R_9 independently represents _ commit 13 group, _s〇Ri3 group, -s(0)2r13 group, _s(0)2NRl3Ri4* group, ·NRi3S(〇)2Ri4 group, -NR13S(0)2NR14S111, - 〇R13 group, _c(〇)〇u group, 〇-C(o)R13 group, _c(0)_(CH2)n_Ri3 group, _NRi3R" group, -C(0)-(CH2) n-NR13R14 A® > -NRi3C(0)-(CH2)n-R14 •NR^OHCmNRHR]5 groups, each of which is n Or i or 2; or in the presence of two adjacent -CR9 groups, two adjacent _CR9 groups and their bonded carbon atoms optionally form a C5_Ci2 aryl group or a 4 to 12 membered heteroaryl group a cycloalkyl or heterocyclic group, the heteroaryl group and the heterocyclic group containing at least one hetero atom selected from the group consisting of 0, S and N, the aryl group, the heteroaryl group, the cycloalkyl group and the heterocyclic group being not Substituted or substituted by one or more selected from the group consisting of a _ prime atom, a linear or branched Q-C6 alkyl group, a monocyclic or polycyclic C5_Ci4 aryl group containing at least one hetero atom selected from the group consisting of ruthenium, S and N An aryl group, or a substituent substituted with at least one hetero atom of 5 to 14 36 201130835 member selected from the group consisting of o, s, and N, wherein the aryl group, the aryl group, and the hetero aryl group And the heterocyclyl substituent is unsubstituted or substituted with a plurality of substituents selected from the group consisting of a dentate atom, a thiol group, an aryl group, a linear or branched alkyl group, or a cvq haloalkyl group; R·5 represents a hydrogen atom, a linear or branched chain CrC6 alkyl group, and the alkyl group is optionally selected from one or more selected from the group consisting of a hydroxyl group, a cyano group, a Crc4 dentate alkyl group, a crc4 hydroxyalkyl group, and a C3-C1G cycloalkane. , phenyl or 6-membered saturated] substituted with a substituent of the heterocyclyl ring or R5 represents a -S(0)2R1 fluorenyl group, a fluorenyl group, a -C(O)OR10 group, _c(〇)- (CH2)n-R1() or -οχοχαΗ^-Νΐ^ι^ groups; R6 and R7 each independently represent a hydrogen atom, or a linear or branched Q-C6 ray group, which is optionally subjected to a Or a plurality of substituents selected from the group consisting of a thiol, a cyanohydrin, a CrC4-alkyl group, a CrC4 hydroxyalkyl group, a crc4 alkoxycarbonyl group, a C3_C7 cycloalkyl group, a benzyl group or a 6-membered saturated N-containing heterocyclic ring; R8 represents a hydrogen atom; a hydroxyl atom; a gas group; a linear or branched bond c _c alkyl group; a c2-c4 alkenyl group; a c2-c4 alkynyl group; a Crc4 group; a c group; a 6 group; a Q-Ch) cycloalkyl group; -C1Gcycloalkenyl; monocyclic to diyl; containing at least selected from 0, 1 =; containing at least one selected from 0, S and N 1 to 14 (4) groups; containing a single ring a C5-C9 aryl group or a 5- to 9-membered cyclohexene or heterocyclic group in a double county, wherein::= is bonded to a heteropoly group selected from hydrazine, S, and N = a aryl group or a heterocyclic group. Doped-bicycloalkyl of a charcoal atom or doped with up to 12 fluorenes having up to 12 bicyclic dilute groups, deuterium atoms - 3 7 201130835 wherein the alkenyl group, alkynyl group, functional group, hydroxyalkyl group, cycloalkyl group, cycloalkenyl group, aryl group, heteroaryl group, heterocyclic group, bicyclo group, aza-bicycloalkyl group and aza - a bicycloalkenyl group is unsubstituted or substituted with one or more substituents selected from the group consisting of Ra, -(CVC4 alkyl)-CN group or -(CrC4 alkyl)-C(0)NR'R" group Wherein R· and R" are the same or different and are selected from a hydrogen atom and a linear or branched chain CrCt alkyl group; and the alkyl group is unsubstituted or substituted with one or more substituents selected from Rb; or -SR13 group, -SOR13 group, -S(0)2R13 group, _s(o)2NRi3Ri4 group, -nr13s(o)2r14 group, _nr13s(〇)2nr14 group, -OR13 group, - C(0)0R13 group, _〇_c(〇)r13 group, -C(0)-(CH2)n-Rl3 group, -NR]3R14 group, -C(0)-(CH2) An n-NR13R14 group, a -NR13C(9)-(CH2)n_R14 group or a -NR13C(0)-(CH2)n-NR14R15 group, wherein η is 〇, ! Or 2, or R8 together with the nitrogen atom to which Rs is bonded together form a 4 to 10 membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and which is linear or branched QQ alkyl, single ring Or a polycyclic c5_Ci4 aryl group, having 5 to 14 members of a hetero atom selected from 0, S and fluorene, and 5 aryl groups containing at least one hetero atom selected from the group consisting of ruthenium, S and N M indigenous group, -SOR10 group, -C(〇)仰2)n_Ri〇 group, $-C(〇MCH2)n-NR10Rn group substituted, wherein each n is 〇, i _ A The aryl group, the heteroaryl group and the heterocyclic ring S are substituted by a substituent selected from a slit atom, a cyano group, a cyano group, a linear branched alkyl group, or a CrC4 haloalkyl group, and the chain Cl_C6 is substituted or - or a plurality of substituents selected from the group consisting of the self-priming atom 38 201130835 haloalkyl; the limitation is that when m is 0, R8 is not a -SRn group, a -SOR13 group, a -s(o)2r13 group , _s(〇)2nr13Ri4 group, -nr13s(o)2r14 group, -NR13S(〇)2NR14 group, -OR13 group, -〇-c(〇)Ri3 group, _NRnRl4 group, -NR13C( 0)-(CH2)n-R14 group or _NR13C(0)-(CH2)n-NR14R15 group, among them

Ra is a halogen atom; a cyano group; a hydroxyl group; a linear or branched chain CrC6 alkyl group; a crC4 dentate alkyl group; a crC4 hydroxyalkyl group; a C3-C7 cycloalkyl group or a C3-C7 cycloalkenyl group; a monocyclic or polycyclic C5- a C14 aryl group which is unsubstituted or substituted with one or more spectrin atoms; a 5 to 14 membered heteroaryl group containing at least one hetero atom selected from the group consisting of ruthenium, S and N; containing at least one selected from the group consisting of ruthenium 5 to 14 membered heterocyclic groups of the hetero atom of S, N; -SR10 group; -SOR1() group; -s(o)2r10 group; _s(0)2NRi〇Rii group; ·ΝΚι〇 δ(0)2Κι1 group; -NRl〇S(0)2NRn group; _〇r10 group; ·<:(〇)〇Ϊ110 group; •〇-C(O)R10 group; _c( 〇)_(CH2)n_Ri〇 group; _NRi〇Rn group; group; _NRl〇c(〇)_(CH2)n_R11 group or group, wherein each η is 〇, 1 or 2;

Rb is cyano; crC4 dentate; CrC4 hydroxyalkyl; CrQ cycloalkyl or C3-C7 cycloalkenyl; monocyclic or polycyclic C5-C14 aryl, unsubstituted or via one or more a self-substituted atom; a 5 to 14 membered heteroaryl group containing at least one hetero atom selected from the group consisting of ruthenium, S and N; and a 5 to 14 fluorene heterocyclic group containing at least one hetero atom selected from the group consisting of 〇S and N 〇 〇 1〇 group; -S〇Rl0 group; -s(〇)2R10 group; -s(o)2NR10R"group; 39 201130835 -NRwSPhRn group; -NRh^OLNR"group; R1 〇 group; -C(O)OR10 group; ·〇<(0)Κι〇 group;_C(0)_(CH2)n_Ri〇 group-NR10R"group; -C(O)- (CH2)n-NR10Ru group; '-NR10C(O)_(CH2)n-Rn group or -NR10C(O)-(CH2)n-NRuRl2 group, wherein n is 0, 1 or 2;

Rio, Rii, and R!2 each independently represent a hydrogen atom, a cyano group, a straight or branched chain CrC0 alkyl group, a CrC4 dentate group, a CrC4 hydroxyalkyl group, an aerobic group 'CVC7 ring alkyl group, a phenyl group, and 1, 2 or 3 5- to 6-membered monocyclic heteroaryl groups selected from the group consisting of hydrazine and a hetero atom of S, having 5 to 6 membered heterocyclic groups containing hydrazine, 2 or 3 nitrogen atoms, containing a monocyclic Cs-C6 aryl group The aryl or heteroaryl group is directly bonded to a bicyclic group of a 5- to 6-membered cycloalkyl or heterocyclic group, and the heteroaryl or heterocyclic group contains 1, 2 or 3 nitrogen atoms, and the halogen group is lightly An alkyl group, a pyrolyl group, a cycloalkyl group, a phenyl group, a heteroaryl group, a heterocyclic group, and a double group are unsubstituted or substituted with one or more substituents selected from the substituents Rc, and the alkane a group which is unsubstituted or substituted with one or more substituents selected from the substituent Rd;

Rc is a halogen atom, a thiol group, a cyano group, a straight or branched chain crc6, a crc4 alkyl group, a crc4 alkoxy group, a crc4 hydroxyalkyl group, a C3_C7m alkyl group, a phenyl group, and contains 1, 2 or 3 nitrogens. a 5- to 6-membered monocyclic heteroaryl group of an atom having 5 to 6 membered heterocyclic groups of 1, 2 or 3 nitrogen atoms or containing 1, 2 or 3 nitrogen atoms (VC? heterocycloalkyl ketone) The phenyl group is unsubstituted or substituted with one or more dentate atoms, and the heteroaryl, heterocyclic, and heterocycloalkyl ketone groups are unsubstituted or have one or more straight or branched chains (^-(:3 alkyl substitution; 201130835

Rd is a nitrogen group, c "C4 functional group", 跪oxy 'Ci-C4 —... group, CrC7 cycloalkyl, phenyl group, containing 1, 2 or 3 nitrogen atoms, especially 5 to 6 members of a single ring An aryl group having 5 to 6 membered heterocyclic groups of 1, 2 or 3 nitrogen atoms or a C3-C7 heterocycloalkyl ketone group having 1, 2 or 3 nitrogen atoms which are unsubstituted or Substituted by one or more halogen atoms, and the heteroaryl, heterocyclic and heterocycloalkyl ketone groups are unsubstituted or substituted by one or more or branched chain CrC3 alkyl groups; the bond R 3, R 4 and R 5 each independently represent a hydrogen atom, a cyano group, or a branched chain CVQ alkyl group, a CrQi|alkyl group, a CrC4 hydroxyalkyl group, a c-bond alkoxycarbonyl group, a Q3-C7 cycloalkyl group, a monocyclic or polycyclic ring. a c5_Ci4 aryl group, jC4, at least one 5- to 14-membered heteroaryl selected from the group consisting of 0, s, and N heteroatoms having 5 to a % group of at least one hetero atom selected from the group consisting of ruthenium, s, and N, wherein a calcinyl group, a pyrolyzed group, a pyrolyzed base group, a cyclamate group, a benzyl group, a heterocyclic group, and a heterocyclic group are unsubstituted or substituted by a plurality of substituents, and the alkyl group is optionally used. Substituted by a substituent of the base. In the compound of formula (I): the same or different and each surface atom atom, 11⁄2 base, cyano group, linear fluorene branched chain Ct-γ^ primogen or CVQ hydroxyalkyl; residue, Cl_C• Base 1 ^ table ^ hydrogenogen, sub., dentate atom, warp group, gas base, bond cvc6 leucoyl, Crc4 tooth burnt group, Crc4 " ^ knife branch, 5 to 10 member heterocyclic group, C6-Ciq Aryl, 5: '3:1 〇 ring-burning '扉, group or Na R"R... group, the ring-burning group, the impurity =, 201130835 ΐίΓί heteroaryl without taking one or more cans Atom, or a linear alkyl group, an aryl group or an oxime I chain c: R"r or different and each represents an ammonia atom, !6 alkyl, Cl-C4 _alkyl or Crc4 hydroxyalkyl; bond cr5c6 H Or branching thereof - (c3 C di-, 4 CrQ-alkyl or - (CA burn: form ' or R5 together with the nitrogen atom bonded by R8 and R5 is a hetero atom and the == it contains - or Two nitrogen atoms are used as early S + yl groups unsubstituted or contain one or two nitrogen or a heteroaryl group, -ccoxci^ni & u % rid branched chain crQ alkyl, (d)-alkyl, c& :=±' and r,, and r,,, the same or different and each represents a hydrogenogen 3 77 bond C "C6 wire , Crc4 i silk or Crc4 is burned, silk / Π117 is the same or different and each represents a hydrogen atom, a linear or branched ϋI f, a 院南院 base, (4) a burnt group or a - (QQ 炫基)-Het_ (CrC4 alkane 1) hydrogen, sub, _ atom, meridine, aryl, linear or branched Qc^ group, CrC4 silk group, CrC4 — group, (d) burnt group, 'C3_i^, burnt base, 5 to a 10-membered heterocyclic group or a 5- to 6-membered heteroaryl group which is unsubstituted or is halogenated by one or more halogen atoms, or a straight di- or pyridyl group, a nitrogen group, a thiol group, or a Cl_C4 group. Oxygenate' or R? is a -Het-R, Y,-R, ', or -C(0)-Het-R丨 group, 42 201130835 or in the presence of two adjacent -CR9 groups The two adjacent _CR9 groups and the carbon atoms to which they are bonded optionally form a CVC1Q aryl group which is unsubstituted or one or more selected from a halogen atom, a linear or branched chain Ci_C6 alkyl group. Substituted by a substituent of a radical or a crc4 alkoxy group;

Rs together with R_5 and a nitrogen atom bonded to the uldent 5 to form the 5- to 9-membered heterocyclyl ring ' or Rs is a hydrogen atom; a linear or branched chain CrC6 alkyl group; CrC4-alkyl group; CrC4 hydroxyalkyl group; C3_Ciq cycloalkyl; 5 to 1 member heterocyclic group; 4 to 10 membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms, said ring being substituted by one, two or three pendant oxy groups; C6 -C1G aryl; 5 to 10 membered heteroaryl; -L-Het-R,"; -LA; -AS〇2-R,; -A-SO-R",; -A-A'; -ALC (〇)NR,R" ; -AL-CN ; -AC(0)-Het,-L-CN ; -AC(0)-NR'R" ; -A-C(9)Z-An ; -AC(0)- R,n ; -AC〇2-R,; -AC(0)z-L_An' ; -AC(0)zL-CN ; -AC(0)-A'-A"; -AC(0)-LR ' ; -AC(0)-L-CN ; -A-Het-L-CN ; -AC(0)-L-Het-A? ; -AC(0)-L-Het-LA' ; -AC( 0)-L-Het-LR"'; AC(0)-L-Het-C(0)-A'; or -AC(0)zL-Het-R' group, wherein z is 1 or 2, R, and R" are the same or different and each represents a hydrogen atom, Cr(:4-alkyl, CrC4 hydroxyalkyl, or a straight or branched chain CrC6 alkyl group which is unsubstituted or alkoxy or 5 or 6 membered heterocyclic groups substituted, and R," And represents a straight or branched chain crc:6 alkyl, crC4 dentate or cn_C4 hydroxyalkyl, said heterocyclic group being fused to a phenyl group as the heteroaryl group, and wherein said cycloalkyl group, heterocyclic ring a base, an aryl group, and a heterofilament unsubstituted or substituted with or a plurality of atomic atoms, via a f cyano group, a crC4 alkoxy group, or a straight or branched chain Ci_C4 alkyl group, 43 201130835 Or substituted by a cyano group, and wherein L is a linear or branched bond CrQ stretching group, or two hydroxyl groups are substituted, octa, A substituted Ge, left ~ linear, and taken, wherein R is a hydrogen atom , chain chain branched crC4 wire, CrC4 fluorenyl group γ represents -c(〇)-, so or s〇2, A. ί to = and A,,, the same or different and each represents (d). Cycloalkane; 4 to 10 containing 2 or 3 nitrogen atoms = clothing =, the ring is substituted by one, two or three pendant oxy groups; 1G doped aryl ί contains a monocyclic aryl group or a heterocyclic ring to a bicyclic group of 6-membered cyclodextrin or a heterocyclic group, said di-, hetero-basic, aryl, heteroaryl, and bicyclic group unsubstituted or via: or a sulfonium atom, a thiol group, a cyano group, a straight Chain or branch chain CA burning , CrC4 from alkyl, Cr (: 4 hydroxyalkyl or a substituted alkoxy Crc4. Typically, in this embodiment, in the compound of formula (I):

Ri, R2 and R4 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a linear or branched chain CrC6 alkyl group, a Crc4 haloalkyl group or a crc4 group; and R3 represents a hydrogen atom, a dentate atom, Meryl, cyano, linear or branched bond Ci-C6 alkyl, Cl_c4 dentate, crc4 light alkyl, c3_Ci anthracene ^5 to 10 membered heterocyclic, G-Cio aryl, 5 to 1 a heteroaryl, f(O)OR* group or a -C(0)NR"R," group, said cycloalkyl, heterocyclyl, aryl and heteroaryl being unsubstituted or Passing one or more of the south atom atoms, or a straight or branched chain crQ6 group, a trans group, a cyano group or a cvc4 alkoxy substituent, the 201130835 generation 'where R, R' and r·' are the same or different and each represents hydrogen Atom, linear or branched chain CrC6 alkyl, Crc4 dentate or crc4 hydroxyalkyl; R5 represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a linear or branched bond CrQ^ group, a CrQ dentate group, a Cl_C4 An alkyl or -(C)-C4 alkane f XCH: 7 cycloalkyl), or Rs together with Rs and a nitrogen atom bonded to form a 5 to 9 membered saturated heterocyclic group - which contains - or two nitrogens Atom as a hetero atom The heterocyclyl ring is unsubstituted or substituted with a _c(〇)_(CH2)n_R• group or a —_C(J3HCH2)n-NR"R" group, wherein n is 〇, 丨^ represents hydrogen Atom, or a straight or branched chain ^^6 alkyl, ^-haloalkyl,

CrQ hydroxyalkyl or cyano 'and R' and Rm are the same or different and each represents a hydrogen atom, a straight or branched chain CrQ alkyl group, a CrQ dentate group or a crC4 hydroxyalkyl group; K and & are the same or different and each Represents a hydrogen atom, a straight or branched chain crc6 alkyl group, or a CrC4 dentate alkyl group, or a CrC4 hydroxyalkyl group; the heart is a hydrogen atom, an imine atom, a hetero, a cyano group, a linear or branched bond C1-C6 alkyl group, a crc4 haloalkyl group, a Crc4 hydroxyalkyl group, a 5 to 10 membered heterocyclic group or a 5 to 1G membered hetero-methyl group, and a heterofilament unsubstituted or via one or more halogen atoms, or a straight or branched chain Substituting a crc6 alkyl group, a cyanide group, a benzyl group or a Crc4 group substituent, or in the presence of two adjacent groups, the two adjacent CR9 groups and the carbon atoms to which they are bonded The case forms a c6_c1G aryl group which is unsubstituted or substituted with a plurality of substituents selected from a pixel atom, a straight branch chain Ci_C6^, a green or a group; R8 together with a nitrogen atom bonded by I and R5 forms 5 to 45 201130835 c 'rrc, c6. crc4 haloalkyl, / hydroxyalkyl, c3_CiG ring, 5- to cyclo, C6-C10 aryl, 5 to 10 membered heteroaryl, Cut (4) "," -A-SO.-R- > -A-SO-R- , .AA-. -ALC(〇)NRtR,. .λ.^^ ' -AC(0)-Her-L -CN, _A_C(9) tear R", -AC(0)-R", -A-CCVR,, _Α·αο) _τ Απ, or _ eight like 'group, where / is _, = same or different And each represents a hydrogen atom, or a linear or divided and I phase QQ alkyl group, (να fluorenyl or (tetra) hydroxyalkyl group, the chain f heteroaryl fluorenyl group is fused, and its , miscellaneous ^ square base and miscellaneous unsubstituted or - or a plurality of _ atom:, enchanted earth, linear or branched chain oxy, soil, L is a linear or branched chain CrC6 alkyl; Double ~ pit base, (VC4 halogen group *CrC4 A, A, A" and A"' are the same or different and each group, 5 to K) member heterocyclic group, C6_Ci () aryl group or 5 to, burn a heterocyclic group, a heteroaryl group, and a heteroaryl group unsubstituted "hetero = _ atom, a hydroxy group, a cyano group, a straight bond or a branch ^ or an oxime alkoxy group. A knife hard ~ alkyl 4Cl_C4 d'D and ~ The same or different and each represents a hydrogen atom, an atom or a domain, or a straight or branched chain Ci_c46 group and r4 preferably each represents money. 1, 2 46 2011308 35 Typically, R_3 represents a hydrogen atom, a halogen atom, or a thiol group, a cyano group, a linear or branched chain CrQ group, a CVC6 cycloalkyl group, a stupid group, a 5 to 6 membered heteroaryl group, a C(0)0R' or a -C(0)NR,,R"' group, the alkyl group, the phenyl group and the heteroaryl group are unsubstituted or have 1, 2 or 3 halogen atoms, or a linear or branched CrC2 alkyl group, Substituted with a hydroxy, cyano or CrC2 alkoxy substituent, wherein R', R" and R," are the same or different and each represents a hydrogen atom, or a straight or branched chain CrC2 alkyl group. Preferably, R3 represents a hydrogen atom, a halogen atom, or a chaotic group, C; 3-C4%-alkyl, a base, a π-bite group, an n-salt group or a c(〇)〇R group; The phenyl group, the pyridyl group and the pyrazolyl group are unsubstituted or substituted by a hydrazine or a 2-amino group, and the towel R thereof represents a hydrogen atom or a linear or branched bond CrC2 alkyl group. In general, Rs represents a hydrogen atom, a halogen atom, or a hydroxyl group, a linear or branched CA group, or a _ (Cl_C4 alkyl KCrC6 cyclod), or a ruthenium, together with a nitrogen atom bonded to R8 and R5, forms 5 a 7 M saturated heterocyclic group containing - or two nitrogen atoms as a hetero atom and the heterocyclic ring unsubstituted or via -C(9)-(CH2)nR, ((〇Μαΐ2)η视T, Or a 5-membered heteroaryl group, wherein η is 0 or R, meaning that the chlorine atom is a di- or straight-chain or branched chain (VQ, K, and R" and Rn, the same or each of which represents a hydrogen atom, or a straight or branched chain CrQ filament. More than L' or a linear or branched bond CrC4 alkyl group, or _(CrC4 alkyl)_(C3_C6 ring group), or a nitrogen atom of a 3 junction To 7-membered saturated heterocyclic group II^^-0(0)-(€Η2)η^5ΐ.〇(〇)^^ ; ^ 201130835 aryl substituted 'where η is 〇 or 1 ' R' represents a hydrogen atom, Or a straight or branched chain, a core, or a cyano group, and R, m R", the same or different and each having no hydrogen atom, or a straight or branched chain CrC4 alkyl group. Preferably, R5 represents a hydrogen atom. Or burning through a base, straight chain or branched chain crc2 Or -(crc2 alkyl Wc3-c4 cycloalkyl), or R5 together with R8 and the nitrogen atom to which Rs is bonded together form a 7-membered heterocyclyl ring containing one or two nitrogen atoms as a hetero atom, The heterocyclyl ring is unsubstituted or substituted with a -c(o)-ch2-r' group, which + R represents a straight or branched bond Ci C2 alkyl, or a cyano group, -C(〇)-CH2- a NEt2 group or a pyridyl group. More preferably, Rs represents a hydrogen atom, or a hydroxyl group, a linear or branched alkyl group, or a -(CrC2 alkyl)-(CrC4 cycloalkyl group), or Rs together with a heart and a bond of r5 The nitrogen atoms of the knot together form a 7-membered heterocyclyl ring containing one or two nitrogen atoms as a hetero atom. The heterocyclyl ring is unsubstituted or substituted with a group of _C(〇)_ch2_r, where R' Indicates a straight or branched chain CrC2 alkyl group, or a cyanoguanidine. Usually 'R0 and R7 are the same or different and each represents an argon atom, a linear or branched Q-C4 alkyl group or a (CrC2 alkyl)-0- (CrC2 burned). More generally, 'R_6 and R7 are the same or different and each represents a hydrogen atom, or a straight or branched bond C1-C4 alkyl group. Preferably, Rs and R/7 are the same or different and each represents a hydrogen atom, or CrC3. Alkyl or methoxy More preferably, 'R6 and R7 are the same or different and each represents: an atom or a CrC2 alkyl group. Usually 'R9 is a hydrogen atom, a halogen atom, or a hydroxyl group, a linear or branched Q-C4 alkyl group, CVC4 is burned. An oxy group, a C3_C7 ring-based group, a 5- to 6-membered heterocyclic group or a 5- to 6-membered heteroaryl group, said heterocyclic group and a heteroaryl group being unsubstituted or 48 201130835 via 1, 2 or 3 halogen atoms, or Substituting a straight or branched chain CrC4 alkyl, carboxyl or CrC4 alkoxy substituent, or in the presence of two adjacent 〇^ groups, the two adjacent _Cr9 groups and their linkages The carbon atom optionally forms a benzene ring which is unsubstituted or substituted by 2 or 3 substituents selected from a halogen atom, or a linear or branched chain CrC2 alkyl or CrC2 alkoxy substituent, or R9 is - Het_R,, Y'-R, " or -C(0)-Het-R, a group. More generally, 'R_9 is a hydrogen atom, a halogen atom, or a radical, a straight or branched bond CrQ alkyl group, a 5 to 6 membered heterocyclic group, or a 5 to 6 membered heteroaryl group, said heterocyclic group and a heteroaryl group. Unsubstituted or substituted with 1, 2 or 3 gram atoms, or a linear or branched chain CrC4 alkyl group, or a CrC4 alkoxy substituent, or in the presence of two adjacent -CR9 groups, Said two adjacent _ 匸 9 groups and the carbon atoms to which they are bonded form a benzene ring, which is unsubstituted or 1, 2 or 3 selected from a halogen atom, or a linear or branched crc2 alkane. Substituent substituted with a substituent of a CrC2 alkoxy substituent. Preferably, R9 is a hydrogen atom, a halogen atom, or a CrC2 alkyl group, a carbazine, a pyridone or a pyridyl group. The piperazine, pyridone, and a pyridyl group are unsubstituted or have 1 or 2 dentates. Substituted by an atom or a CrC2 alkoxy substituent, or 119 is a -1^-11', Y,-R''' or -C(0)-Het-R' group, or in the presence of two adjacent-CR9 In the case of a group, the two adjacent _CR9 groups and the carbon atoms to which they are bonded, as the case may be, form an unsubstituted benzene ring. More preferably, the heart is a hydrogen atom, a halogen atom, or a CrC2 alkyl group, an n-pyridyl group or a pyridyl group, the piperazine, pyridone, and pyridyl group are unsubstituted or 1 or 2 Substituting an imine atom or a CrC2 alkoxy substituent, or in the presence of two adjacent -CR9 groups, the two adjacent -CR9 and the carbon atom of the bond 49 201130835 are formed as appropriate Replace the benzene ring. Usually, in the compound of the formula (I), r8 represents a linear or branched bond group, a CrC4 functional group, a CrC4 hydroxyalkyl group, a c3-C10 cycloalkyl group, an aryl group, and contains 1, 2 or 3 selected from N. 5, 10 membered heteroaryl groups containing 1, 2 or 3 heteroatoms selected from N, 0 and S contain 1, 2 or 3 a 5 矣 7 membered heterocyclyl ring of a nitrogen atom, the ring being substituted with one or two pendant oxy groups, or Rs is -L-Het-R''', -LA, -AA, _A-LC (〇 )NR, R", -AL-CN _A-C(0)-Het'_L, CN, _A-C(0)-NR'Rn, -AC(0)zW, -AC(0)-R'&quot ; ' -A-CO2-R'' -AC(0)zL-A'M >-AC(0)z^-^'" ' -AC(0)zL-CN , -AC(0)- A'-A"> -AC(0)-LR' -AC(0)-L-CN, -A-Het-L-CN, -AC(0)-L-Het-A', -AC( 0)-L-Het-LA', -AC(0)-L-Het-L-RM, AC(0)-L-Het-C(0)_A' or -AC(0)zL-Het- R' group, wherein z is 1 or 2, R| and R" are the same or different and each represents a hydrogen atom, or a straight or branched chain CrC6 alkyl group, which is unsubstituted or substituted (^(^) An oxy group, or a 5 or 6 membered heterocyclic group, a QQ halogen group or a crC 4 hydroxyalkyl group, and

Rm represents a linear or branched chain Cl-C6 alkyl group, a CrC4 haloalkyl group or a CrC4 hydroxyalkyl group, and the heterocyclic group and the heteroaryl group are optionally fused with a phenyl group, and wherein the cycloalkyl group, the heterocyclic group The cyclo, aryl, and heteroaryl groups are unsubstituted or substituted with one or more substituents selected from halogen, atom, thio, cyano, straight or branched chain, or CrC4 alkoxy, said alkane The base is unsubstituted or substituted with a chaotic group. More typically, in the compounds of formula (I), Rs represents a straight or branched chain 50 201130835

Crc6 alkyl, CVC4 dentate alkyl, Cl_c4 hydroxyalkyl, 〇3-(:10 cycloalkyl, C6_c1()aryl, containing 1, 2 or 3 heteroatoms selected from N, fluorene and s 5 to a 10-membered heteroaryl group having 5 to 1 member heterocyclic group '_L-Het-R,", -LA, -Α·Α, containing 1, 2 or 3 hetero atoms selected from ruthenium, osmium and s, 'ALC(0)NR'R" , -AL-CN j -AC(0)-Het'-L-CN ^ -ac(o)-nr'r",_A_c(〇)z_A",_A_C(0) _R,",A c〇2 R| -ac(o)zl-a'",-A-qoM-R''·,_a_c(0)z_L cn or _AC(0)zL-Het-R' a group wherein z is i or 2, R, and R, which are the same or different and each represents a hydrogen atom, or a straight or branched chain Crc6 alkyl group, a crc4 haloalkyl group or a CrQ hydroxyalkyl group, and R" represents straight a chain or branched chain Ci_C6 alkyl, CrC4 i alkyl or CrC4 hydroxyalkyl, said heterocyclic group and heteroaryl optionally being fused to a phenyl group, and wherein said cycloalkyl group, heterocyclic group, aryl group II And the heteroaryl group is unsubstituted or substituted by a plurality of selected from a halogen atom, a hydroxyl group, a cyano group, a linear or branched chain CrC4 alkyl group, or a CrQ alkoxy group. Typically, L is a straight chain or Branch chain CrQ extension Or, it is substituted with a two-sided group. More usually, L is a linear or branched chain, and a terroir. Preferably, L is a linear or branched chain CrC: 5 alkyl group, and both her silk generation. More preferably, L For the straight-button shirt, often 'Het means 〇 or NR and gamma, indicating bribe atom, karma or centrifugation CrC4^ $

Het represents NR, wherein, 丄 ^, is a hydrogen atom, or a linear or branched chain crC4 is preferably a hydrogen atom, or a straight or branched chain Ci_C2. H means Ο, ΝΗ or N(CH3). Better than Het said. Y is usually a so2 group. Typically 'A, A, A, and A,' are the same or different and each represents a ring-based, 5- to 6-membered heterocyclyl, 1-oxime, phenyl, 5- to 9-membered heteroaryl, said ring An alkyl group, a heterocyclic group, a stupid group, and a heteroaryl group which are unsubstituted or mechanized, 2^3 i atoms, or a thiol group, a cyano group, a linear or branched chain group, a crc2 filament, and a Cl_C2 Or Ci_C2 alkoxy substituted. Four more usually, A, A, A, and A", the same or different and each represents A%, alkyl, 5 to 6 membered heterocyclic, phenyl, 5 to 6 members Heteroaryl, the cycloalkyl, heterocyclic, phenyl, and heterochloro unsubstituted neon 2 or 3 ^ sulphide atoms, or thiol, cyano, linear or branched CVC2, or Crc2 alkane Oxygen substitution. Usually 'A is a 5- to 6-membered heterocyclic group, a 5- to 6-membered heteroaryl group, a phenyl$C3-C6 cyclofilament', a heterogeneous, a heterozygous, a benzene wire, and a cycloalkyl group = substituted or via 1, 2 Or 3, preferably 1 or 2, atoms or substituted groups. More usually, A is a 5- to 6-membered heterocyclic group, a phenyl group, a CVQ-Wei group, a singular ring-green unsubstituted, 2 or 3, preferably i or 2 self-atomic atoms or a thiol or c "c2 substituted. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . More preferably, 'A is a base group, a phenyl group or a cyclohexyl group which is unsubstituted or substituted by a c]_c2^ group. 52 201130835 Typically, A' is a CVC6 cycloalkyl group, a 5, 6 or 9 membered heteroaryl group, a 5 to 6 membered heterocyclic group, an extremity or a stupid group, said cyclofilament, heteroaryl, heterocyclic group, 10 The alkyl or phenyl group is unsubstituted or substituted with a 2 or 3 atom, or =, a Crc2 alkyl group, a CrC2 group, or a CrC2(tetra)dioxamethyl group. More usually, A, is a phenyl group, which has no = 2 or 3 dentate atoms, or a cyano group, a trans- or a phenyl group, and A' is a phenyl group. Or two alizarin-substituted, methoxy or cyano substituted; C3_Q cycloalkyl, which has not been substituted with a _ atom, a benzyl group, a methyl group or a trifluoromethyl group; substituted or substituted with a methyl group The earthen group is not in the same material. The group is 'unsubstituted or substituted by one or two diterpene atom; ° lead group; tetrahydrogen chelate group; Μ ', earth group, buckle An alkyl group; a tetrazole group; a thiazole group, a generation or a cyanamide extract. 彳„ ^ Lane I group, which has not been substituted with a murine group or a dioxolane- or two Methyl substitution. More preferably, ^ is substituted or substituted by 1 or 2 self-atomic atoms or cyano groups. #,未, !substituted or via or 5 to 6 member 嶋, team Wei, phenyl, substituted or ^ The base is not 2 or 3 halogen atoms, or the cyano group, the base is more usually, the human is 5 to earth or Q-Cj, 2 to 6 is substituted, the cycloalkyl is substituted by d or 1, 2 Or 3 Nansu and Hetero-square groups are not substituted by the base. , ', / Cyanide Or CrC2 alkane 53 201130835 Preferably, 'A' is a slightly filamentous, cyclopropyl phenyl group, the precipitation base, the ruthenium and the base are unsubstituted or ruthenium or 2 dentate atoms or cyanide Substituted. More preferably, A" is a transamination, a cyclopropyl or a (tetra)yl group. The anthracene, a cyclopropyl group and a (iv) group are not substituted with two halogen atoms or a cyano group. / Usually, A''' is 5 To a 6-membered heteroaryl group, the heteroaryl group is unsubstituted or substituted with 2 or 3, preferably 1 or 2, or a thiol or a Ci_C2 group. a heteroaryl group which is unsubstituted or substituted by 1, 2 or 3, preferably 1 or 2 dentate atoms or a hydroxyl group or a CrQ alkyl group. One A...preferably an imidazolyl group. A"' More preferably it is an imidazolyl group. Typically, R8 together with the nitrogen atom to which Rs and Rs are bonded together form the 5 to 7 membered ring-based ring ' or Rs is a hydrogen atom, or a straight or branched chain Ci_C6 alkyl group, CVQo cycloalkyl group, 5 to 6 members Heterocyclic group, phenyl group, 5- to 6-membered heteroaryl group, -L-Het-R'", -LA, -AS〇2-R', -AA·, -ALC(0)NR 丨R'' , -AL-CN, -AC(0)-Het, -L-CN, -AC(0)-NR'RmI, -AC(0)-A", -AC(0)-R'M, _A- C(0)-L-A"丨, -AC(0)-L-CN, -AC(0)-A'-A 丨', -AC(0)-LR', -AC(0)-L -CN , -A-Het-L-CN , -AC(0)-L-Het-A' , -AC(0)-L-Het-LA' , -AC(0)-L-Het-L- R'"AC(0)-L-Het-C(0)-A' or -AC(0)-L_Het-R' group, wherein R' and r" are the same or different and each represents a hydrogen atom, CrC2 i alkyl, QQ hydroxyalkyl, or linear or branched bee CrC6 alkyl, or 5 or 6 membered heterocyclyl, said alkyl being unsubstituted with CrC2 alkane 54 201130835, R,, representing a straight chain or a branched chain Ci-C6 alkyl group, a CrC2 haloalkyl group or a Crc4 hydroxyalkyl group, said 5- to 6-membered heterocyclic group being optionally fused to a phenyl group, and wherein said cycloalkyl group, heterofluorenyl group, phenyl group and Heteroaryl Substituted or substituted with i, 2 or 3 dentate atoms, or hydroxy, cyano, CrC2 alkyl or CrC2 alkoxy, and L, Het, Het', A, A', A, and A,,, More generally, Rs together with the nitrogen atom to which K and R5 are bonded together form the 5- to 7-membered ring-based ring, or Rs is a hydrogen atom, or a linear or branched chain CrC6 alkyl group, C6-C1 () cycloalkyl, 5 to 6 membered heterocyclic, phenyl, 5 to 6 membered heteroaryl, _L_Het-R''', -LA, _A-S02-R, -AA, -ALC(0 )NR'R", -AL-CN, -AC(〇)-Het, -L-CN, -A-CW-NR'R"1, -AC(0)-A", -A_C(0)_R ,,,, -AC(0)-L-A''', -AC(0)-L-CN or -AC(0)-L-Het-R' group, wherein R' and R" are the same or Different and each represents a hydrogen atom, or a linear or branched chain CrC6 alkyl group, a crC2 haloalkyl group or a CrC4 hydroxyalkyl group, r,, represents a straight chain or a branch, a CrC6 alkyl group, a Cl_C2_alkyl group or a Crc4 hydroxyalkyl group. The 5- to 6-membered heterocyclic group is optionally fused to a phenyl group, and wherein the cycloalkyl, heterocyclic and heterofilaments are unsubstituted or have 2 or 3 halogen atoms or a trans group, a cyano group. , Ci-C2 burning base or C i-C2 is alkoxy substituted, and L, Het, Het', a, A, a" and A, ' are as defined above. , preferably, together with the nitrogen atom to be bonded, form the 7-membered heterocyclic ring 'or & is a straight or branched chain alkyl group, C3_C6 clothing, a crucible base, an 11 bottom bite, Phenyl, ° than bite, Π Π each bite _, σ than bite, tetrahydro quinone, sulphonyl, -L-Het-R",, -LA, -A-S02-R', 55 201130835 -AA' >-ALC(0)NR'R"> -AL-CN ' -AC(0)-Het'-L-CN > -AC(0)-NR'RMl , -AC(0) -Am , -AC(0)-R ..., -AC(0)-LA,M , -AC(0)-L-CN, _A-C(0)-A'-An , -AC(0)- LR', -AC(0)-L-CN, -A-Het-L-CN, -AC(0)-L-Het-A', -AC(0)-L-Het-LA', -AC (0)-L-Het-LR"· , AC(0)-L-Het-C(0)-A' or -AC(0)-L-Het-R' group, wherein r' and r" Identical or different and each represents a halogen atom, or a linear or branched chain CrC3 alkyl group, which is unsubstituted or substituted by a CrC2 alkoxy group, or a 5 or 6 membered heterocyclic group, and R", represents a linear chain Or a branched chain CrC5 alkyl group, a CrC2 dentate alkyl group or a cvc4 hydroxyalkyl group, wherein the piperidyl group is optionally fused to a phenyl group, and wherein the C3_C6 cycloalkyl group, adamantyl group, piperidinyl group, benzene , pyrrolidine, pyrrolidone, pyridine, tetrahydroquinoline and piperidyl are unsubstituted or substituted by 1 or 2 halogen atoms, or hydroxy, CrC2 alkyl or CrC2 alkoxy, and L, Het, Het, , A, A', A" and A"' are as defined above. More preferably, 'Rg, together with the nitrogen atom to which r5 and r5 are bonded, form the 7-membered ring-based ring, or r8 is a linear or branched chain Ci_C3 alkyl, cyclohexyl, adamantyl, piperidinyl, phenyl , piperidyl, _L_Het_R,", _L_A, -A-S02-R', -A-A', -ALC(0)NR,R", -AL-CN, -AC(0)-Het'-L -CN > -AC(0)-NR'RMl . -AC(0)-Am ' -AC(0)-R',', -AC(0')-LA,,,,-A_C(0) a -L-CN or -AC(0)-L-Het-R' group, wherein R' and R" are the same or different and each represents a hydrogen atom, or a straight or branched chain CrC3 alkyl group, and R" Linear or branched bond C1-C5 alkyl, C1-C2_alkyl or C1-C4 via sleek base, said 0 chen 56 201130835 喃 ΐ 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Anthracene, native and slightly south, unsubstituted or substituted with 1 or 2 dentate atoms, or via, crc2 or CrC2 alkoxy and l, this, this, A, A', A "and A"' are as defined above. The ruthenium is preferably in the compound of formula (1) and is as defined above. In the compound of formula (I), X and γ independently represent a nitrogen atom or _ The CR9 group ', at least one of X and γ, represents a nitrogen atom and is as defined above. When χ represents a nitrogen atom, γ represents a group; when a -CR9 group is represented, γ represents Usually, in the compound of the formula (I), R1 represents a hydrogen atom, a dentate atom, a thiol group, a cyano group, a linear or branched chain Ci_Ce alkyl group, a dentate alkyl group, a C:, an alkyl group, and a CrC4 oxygenated gas. Base, QQ aerobic acid group, C3_C7 cycloalkyl, this group, pyridyl group, 6-membered saturated N-containing heterocyclic ring, _c(0)0Ri3 group® ' ___(〇^13 group, ship i3Ri4 group or -^〇HCH2)n-NRl3R14 group, wherein n, Ri3 and ~ are as defined in the technical formula "1". Preferably, 'Ri denotes a hydrogen atom, a _ atom, an aryl group, a 3 or a branched crc6 group, or a c3_c7 ring, a Ri3Ri4 group, /, a R 3 and a Ru independently represent a hydrogen atom. C3 regulatory basis. Rl preferably represents a nitrogen atom or -NR, 3R = =

Rn and U stand for a hydrogen atom or a linear or branched bond. Ri best represents a hydrogen atom. Usually, in the compound of the formula (I), R2 represents a hydrogen atom, a dentate atom, a secret, a cyano group, a linear or branched chain Cl_C6 alkyl group, a Ci_c4_alkyl group, 201130835

CrC4 decyloxy, C--C-alkyl group, Cl_c4 alkane group, phenyl group, pyridyl group or 6-membered saturated N-containing heterocyclic Durban Banyan hydrogen atom, dentate atom, cyano group, Straight chain or branch;;. = Table J c3-c7 cycloalkyl. More preferably, r2 represents a hydrogen atom or a p-genogen f represents a hydrogen atom. , σσ V丨8 3 clothes not halogen atom, halogen atom, cyano group, linear or branched CVQ alkyl group, CrC4 _ group, Q_c, 4 hydroxyalkyl group, CrQ alkoxy group, CrC4 alkoxycarbonyl group, C3_ group 'containing at least one hetero atom selected from hydrazine, s and N; 6 heteroaryl, or 6-membered saturated N-containing heterocyclyl ring, said alkyl, hydroxyalkyl, alkoxycarbonyl, ring The alkyl group, the phenyl group, the hydroxy group, and the hetero group are unsubstituted or substituted by one or more substituents selected from a halogen atom, a cyano group, a cyano group, or a linear or branched chain CrC6 alkyl group, and The alkyl group is unsubstituted or substituted with one or more cyano groups; or R3 represents a -S(0)2NR13R14 group, a -NR13S(0)2NR14 group, an -ORn group, a _c(o)or13 group, _nr13r14 a group, -NC(0)-(CH2)n-R13 group, -C(〇)_(CH2)n-NR13R14 group, -NR13C(〇)-(CH2)n_R14 group or _NR13C(0 a group of -(CH2)tl-NR14R15 wherein η is 0 or 1, and &3, Rw and R丨5 each independently represent a gas atom, a chaotic, straight or branched chain CrC6 alkyl group, C1-C4 j alkyl, CrQ hydroxyalkyl, CrC4 alkoxy, benzyl, CrC7 cycloalkyl, phenyl or 6-membered saturated N-containing heterocycle Ring. Preferably, R3 represents a hydrogen atom, a halogen atom, a cyano group, a CrC4_alkyl group, a C3-C4 cycloalkyl group, a phenyl group, and contains 1, 2 or 3 hetero atoms selected from N, 〇58 201130835 and s. 5 to 6 membered monocyclic heterocyclic, unsubstituted m aryl unsubstituted "one or more selected from the group consisting of an aryl group, or a straight chain or a branched group, a thiol group, a U^-not-C(0)0Rl3 group or _ (:(〇)仰2)"Weicheng 4 group, S-Γ, 2 3 2 and ~ independently represent a hydrogen atom, a cyano group, a linear or branched chain π 6 = soil, Cl_C4 _alkyl, Cl_C4 a hydroxyalkyl group, a C1_C4 alkoxycarbonyl group, a C3-C7 ring, a phenyl group or a 6-membered saturated N-containing heterocyclic ring. More preferably, the heart represents a hydrogen atom, a functional atom or a cyano group or -C(0) -(CH2)n-NR13R14 group 'where η is 0 or 1 and Ru and Ri4 each independently represent a nitrogen atom, or a straight-chain f-branched chain of Cr (^). The most recorded (iv) liver or cyano group. Usually 'In the compound of the formula (I), r4 represents a hydrogen atom, a dentate atom, a hydroxyl group, a cyano group, a linear or branched chain C1-C6 alkyl group, a Ci_C4 haloalkyl group,

CrQ hydroxyalkyl, CrC4 alkoxy, CrC4 alkoxycarbonyl, C3_C7 cycloalkyl, phenyl, pyridyl or 6-membered saturated heterocyclic ring. The rule 4 preferably represents a hydrogen atom, a halogen atom, a cyano group, a linear or branched chain CrC6 alkyl group, or a CrC4 cycloalkyl group. More preferably, R_4 represents a hydrogen atom. In general, in the compound of the formula (I), r5 represents a hydrogen atom, or a linear or branched chain CrC6 alkyl group, the alkyl group optionally being selected from one or more selected from the group consisting of a hydroxyl group, a thiol group, a direct bond or a "CpC6" group. A pyridyl group, a C1-C4-thingyl group, a C1-C4 hydroxyalkyl group, a CrG group; a cycloalkyl group, a phenyl group or a 6-membered saturated n-heterocyclic ring, and a substituent substitution. R5 preferably represents a hydrogen atom, a linear or branched chain CrC6 alkyl group which is optionally substituted by a CrC7 cycloalkyl group. More preferably, r5 represents a hydrogen atom, or a straight or branched bond crc3. 59 201130835

In the compound of the formula (1), the hydrogen radicals of the formula (1) independently represent a halogen atom, or are unsubstituted or have one or more C: or =,,,,,, preferably, === : "branched chain CrC6 Further, R6 and R7 are more preferably each independently a residual atom, or a linear or branched chain CVC is independently represented by the group, and the R 6 is optimal. Generally, in the compound of the formula (I), 'R9 means gas. Atom, dentate atom, hydroxy, cyano, straight or branched chain crC6 alkyl, CrC4 halo A, C]-C4 alkoxy' CrC7 cycloalkyl, Ci_C4 alkyl _c3-c7 cycloalkyl a 5- to 6-membered monocyclic heteroaryl group containing 1, 2, 3 or 4 heteroatoms selected from N, 0 and s, containing 5 to 7 members of at least one hetero atom selected from the group consisting of ruthenium, s and N a heterocyclic group, wherein the cycloalkyl, phenyl, heteroaryl and heterocyclic groups are unsubstituted or one or more selected from a halogen atom, a hydroxyl group, a cyano group, a linear or branched crc6 alkyl group, _s(〇)2r10 group, _c(0)ORi〇 group, -C(O)-(CH2)-R10 group or 〇〇10 substituent, wherein R1Q represents a hydrogen atom, a cyano group, a straight Chain or branching chain. -. An alkyl group, a C1-C4 halogen group or a C3-C7 cycloalkyl group, which is unsubstituted or one or more selected from the group consisting of a γ atom, a hydroxyl group, a cyano group, a linear chain or a branched chain. CpC: a substituent substituted with a 6 alkyl group or a Ci_c4 halide group; or ~70 K9 represents a -S(0)2Rl3 group, a -RN group ij a typographic group, an -NR^4 group or a _C (〇HCH2)n-NR quinone group, wherein n is 1 and Ru and RM each independently represent a hydrogen atom, a straight chain or a branched chain C丨·& 201130835 alkyl, -(Cl_c4 alkyl)-( (Vc4 alkoxy having γ 少 less one selected from 0, s and or (( ν (: 4 silk > (containing 5 to 7 membered heterocyclic groups to the heteroatom of Lulu); or

In the case of Am I even adjacent groups, two adjacent ·CR

= household ==, sub-cases (4) 5 to 9 members of the aromatic aryl and heteroaryl unsubstituted or substituted by - or a plurality of ^ atom, linear or branched chain CrC4 silk Preferably, 'R9 represents a hydrogen atom, a _ atom, a reduced chain CVQ, a CrC4 from a silk 'Ci_C4 succinyl straight = a base '_CVQ silk · α7 cycloalkyl, phenyl, containing = one selected from N, 0#; 5_S :^汹:js, or 3 has a small white. 5 to 6 membered monocyclic heteroaryl group containing 5 to 7 of each of the hetero atoms selected from o, s, and N, each of the above, a (tetra) group, an alkoxy group, a cycloalkyl group, a phenyl group = heterocyclyl unsubstituted or substituted with _ or a plurality of substituents selected from the atom=base '〇Rio group, wherein R10 represents a hydrogen atom, a cyano group, a straight bond or a branched bond group, and a CrC4 halide Alkyl or c3-c7m alkyl, 1 h埝thesteryl, haloalkyl and cycloalkyl unsubstituted or selected halogen atom, thiol, cyano, linear or branched Μ = or CrC4 Substituted by a substituent of a halogen group; or soil, R9 represents a -S(0)2R13 group, a -(3(0)0^3 group, a _NR group or a -C(〇HCH2)n-NRl3Rl4 group, wherein n is 〇 or i and 3 14 groups and independently represents a hydrogen atom, or a straight or branched chain Cl.. alkane U ^ A * or 61 201130835 in the case of two _CR9 adjacent groups, two The phase, the group and the carbon atom to which it is bonded may form 5 to 9 membered aryl or hetero 9 aryl', and the heteroaryl contains at least one hetero atom selected from the group consisting of ruthenium, S and N. And the heteroaryl group is unsubstituted or substituted by one or more selected from halo, Or the branch chain cvc4^ replaces the silk generation., the branch 5 is good, the nitrogen atom 'dentin atom' is aryl group or the straight chain or c C ^rQ fluorenyl group, CrC7 group, CA alkyl group 7, base 'containing 5 to 6 membered monocyclic impurities of 2 or 3 nitrogen atoms containing 5 to 7 (tetra) ring groups of "2 or 3 nitrogen atoms" "St heteroaryl group and heterocyclic group having no thief- or a plurality of selected groups Substituent substitution, the oxime thereof, represents a hydrogenogen ^ -C_R knife group or R9 represents a ·S(〇)2R13 group, a straight chain or a branched chain two: and ~ independently exfoliated usually, in the compound of formula (1), &; epi-alkyl, Crc4 i-alkyl, _ Γ 甘 Gan,, human knife-type bond h-c6 cycloalkyl, phenyl, naphthyl, containing 6C_C4 alkoxy), c3-Ci.

5 to 6 membered monocyclic heteroaryls of a hetero atom, one selected from the group consisting of N, fluorene, and S 〇 and s. The hetero atom selected from the group consisting of - atomic Γ r 抽 a a 贝 裱 ,, containing 2 or 3 nitrogen The radical directly contains a monocyclic C5.Cd group or a heteroarylaryl group or a heterocyclic group containing a ring group. The heterocyclic ring, stupid, zeoliyl, heteroaryl, heterocyclic group = 62 201130835 ketone And the bicyclic group is unsubstituted or substituted by one or more substituents selected from the group consisting of: a halogen atom; a hydroxyl group; a cyano group; a straight or branched chain crc6 alkyl group, a C1-C4 halogen group, a C3-C7 ring burn a phenyl group which is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group; and contains 1, 2 or 3 hetero atoms selected from N, fluorene and S. a 6-membered monocyclic heteroaryl group which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; 6-membered saturated N-containing heterocyclic ring; -S(O) 2R10 group; -StOhNRwRn group; _NRl〇s(〇)2NRii group; _〇Ri〇 group; _C(0)〇RIO group; _c(〇)_CH2_〇Ri〇 group; -C( O)-(CH2)n-〇-(CH2)mR10 group · -C(O)-(CH2)n-〇_(CH2)m- 〇-R10 base gj ; _c(〇)_(CH2)n_Ri〇 group; -NRwRu group; _c(〇)-(CH2)n_NRi〇R"group; -R,〇C(0)-(CH2 n-NRuR]2 group; _c(CrC4 alkyl VCXOHCHOn-NRwR) group; _(CrC4 alkyl)_CN group or -(Q-C4, group)_c(〇)NR'R" group And wherein R and R are the same or different and are selected from a hydrogen atom and a linear or branched Ci_C4 filament; each of the towels η is 〇 or an integer from 1 to 5, and wherein each of the claws is an integer from 丨 to 3 and wherein 1〇, R„ and R1Z each independently represent a hydrogen atom; a nitrogen group; a linear chain alkyl group; (4) a sister base; a ship base C7 = a soil 'stupid base' _ (Cl_c4 via a hospital base) _ (benzene benzene = or 4 (4) - 5 to 6 heteroatoms; base; containing 1, 2 or 3 nitrogen atoms and 1 or 2 _ groups of μ Λ early ring heteroaryl shout; containing 2 or 3 selected from n 5 to 6 (tetra) ring groups of heteroatoms; or monocyclic CVC6 aryl groups 63 201130835

The cycloalkyl, phenyl, heteroaryl, heteroaryl fluorene, heterocyclic, and bicyclic groups are unsubstituted or substituted with one or more groups selected from the group consisting of: a halogen atom, a surface group; a cyano group; Chain or branched chain CrC6 alkyl; haloalkyl; CrQ alkyl; CrC4 alkoxy; unsubstituted or substituted by one or more elements = subunit; phenyl, 2 or 3 nitrogen atoms Substituted by a substituent of a 5- to 6-membered monocyclic heteroaryl group which is unsubstituted or has one or more straight or branched C1-C3 alkyl groups; or contains 1, 2 or 3 nitrogen atoms Eve; a heterocycloalkyl ketone group substituted, which is unsubstituted or substituted by one or more crc3 alkyl groups; or represents a -s(9)2nr13r14 group, a Νυ(0)2Ν]1ΐ4 group, a -ORu group, a -c(o)or13 group or a _c(0;H:CH2)n_NRi3Ri4 group, wherein each η is G or 卜 and each of Rl3 and Rm independently represents a hydrogen atom; Search for both storms; crc4 phenyl or 6-membered saturated N-containing heterocyclic ring; alkoxy, C3-C7 cycloalkyl; or cyano; linear or branched CrQ filament, unsubstituted or warp Or multiple phenyl substitutions; Cl_c4 —基;CrC4 ship base c together with the nitrogen atoms bonded by R5 and R5

...a VIII wi2vjnr1 〇 Rii base and each R1() and Rn independently represent 64 201130835 hydrogen atom, cyano group, linear or qd w radical, w _ ing base, shell saturated containing N heterogeneous ring, ▲ 3C7 , Stupid or 6 is limited to the group A, preferably 'in formula (1), the CrC4 sulfhydryl or branched chain contains W or 3 selected from N, 〇1G: pit-based 'phenyl,蔡基, m has 2 or 3 selected from dr to 6 members of a single member heterocyclic group, or a 5- to 9-membered cycloalkyl or heterocyclic group containing a hetero atom: or a heteroaryl direct bond The base group contains at least one selected from the group consisting of ruthenium, S and N: hetero-J-heteroaryl or heterocyclic ring, g-alkyl group, oxymethane, glycaryl group, heterocyclic group and bicyclic group. Take ϋΐ - Γί个ΐί

Crc6 alkyl group 'Cl_c4 _ county, C3_C7 Wei, unsubstituted or thin chain or multiple phenyl substituted with self-atomic atoms, containing 2 or 3 _ from N, Q ^ and Sf heteroatoms 5 to 6 members Cycloheteroaryl, 6-membered saturated with 1^heterocyclyl ring, -s(o)2R10 group, _s(0)2NRi〇Rn group, -NR10S(O)2NRu group '-OR1〇 group, _c(〇)〇Ri0 group, -C(O)-(CH2)n-R10 group.,-NR10R„ group, -(^((^-((^^^^^^^^^^^^^^^^^^ a -RwQOHCHzVNRuRij group, a -(CrC4 alkyl)-CN group or a -(CrC4 alkyl)-C(0)NR,R,, group, wherein R' and R" are the same or different and are selected from a hydrogen atom and straight Chain or sub-65 201130835 branching group; wherein η is, and from / two and ~ each independently represents a hydrogen atom, cyano 'straight or branched u, ^ alkyl, c3-c7 cycloalkyl, phenyl, containing h 2 or 3 selected from 5 to 6 membered monocyclic heteroaryl ffi of a hetero atom of jsj, n 0 and S — or 5 to 6 membered heterocyclic groups of 3 nitrogen atoms or containing a single =Q aryl group or The heteroaryl group is directly bonded to a diterpene group of a 6 to 6 membered cycloalkyl or heterocyclic ring containing 1, 2 or 3 nitrogen atoms, 'f-alkyl The alkyl, cycloalkyl, phenyl, heteroaryl, heterocyclyl and bicyclic groups are unsubstituted or substituted with one or more substituents selected from the group consisting of: a halogen atom; a hydroxyl group; a cyano group; a straight chain or a branch Chain crc6 alkyl;

Ci-c: a group of unsubstituted or substituted by one or more halogen atoms; a 5- to 6-membered monocyclic heteroaryl group having 1, 2 or 3 nitrogen atoms, said heteroaryl Unsubstituted or substituted by one or more straight or branched chain Crc3 alkyl ' or a CVC·/heterocyclic compound g synthyl group containing 1, 2 or 3 nitrogen atoms, said heterocycloalkyl ketone group Substituted or substituted with one or more CrC3 alkyl groups; or the heart represents a -S(0)2NR13R14 group, a -NR13S(〇)2NR14 group, a 〇Ri3 group, a -C(0)0R13 group or a C(〇MCH2)n-NR13R14 group, wherein each η is 0 or 1, and each of R13 and Ri4 independently represents a hydrogen atom, a cyano group, a straight chain which is unsubstituted or substituted with one or more phenyl groups or Branched chain Gi-C6 alkyl, CrC4-alkyl, CrC4 alkyl, CrC4 alkoxycarbonyl, C^C7 cycloalkyl, phenyl or 6-membered saturated heterocyclic ring; or R8 bonded together with R5 and R5 The nitrogen atoms together form a 5 to 9 membered saturated heterocyclic group which contains one or a rain nitrogen atom as a hetero atom and which is passed through 66 201130835 <(ο)_(〇ί2)η410 group or _c(〇MCH2) n NRi〇Rii group substituted, where η is 0 or 1' and Riq and R n independently represents a hydrogen atom, a nitrogen group, a straight bond or an oxime chain branched CrC6, a CrC4 i burnt group, a crC4 burnt group, a c"c4 oxygenated wire, a C3_C7 cycloalkyl group, a phenyl group or a 6 member saturated n The heterocyclic ring is limited in that when m is hydrazine, R8 is not a group of 4, a group of -NR^O) 2: ^ 4 or a group of -ORR3. More preferably, in the formula ( In the compound I), r8 represents a linear or branched chain CrC6 alkyl group, a crc4 halogen group, a crC4 alkoxy group, a crC7 cycloalkyl group, an adamantyl group "phenyl group", and contains 2 or 3 selected from N, anthracene and a 5- to 6-membered monocyclic heteroaryl group of a hetero atom of s, a 5 to 7 membered heterocyclic group containing 2 or 3 hetero atoms selected from N, hydrazine, and S, or a phenyl group directly bonded to contain at least a bicyclic group of a 5- to 7-membered heterocyclic group selected from the group consisting of a hetero atom of hydrazine, s, and N, said alkyl group, i-alkyl group, alkoxy group, cycloalkyl group, adamantyl group, phenyl group, heteroaryl group And the heterocyclic group and the bicyclic group are unsubstituted or one or more selected from the group consisting of a halogen atom, a hydroxyl group, a straight or branched chain Ci_C6 alkyl group, a phenyl group, a tonyl group, a -S(〇)2R10, a -C(O) )〇R10, _C(0)_(CH2)n_Ri〇, _NRi〇Rii group, {(OXCHJn-N) a substituent substituted with a RioR^ group, a _(CrC4 alkyl)-CN group or a -(CrQ) group-C(0)NR'R'' group, wherein r' and R" are the same or different and are selected from a hydrogen atom, and a linear or branched chain; wherein n is 〇 or 1, and

Rio and R" each independently represent a hydrogen atom, a cyano group, a linear or branched chain CrC6 alkyl group, a crC4 haloalkyl 'C3-C7 cycloalkyl group, a phenyl group, containing 1, 67 201130835 2 or 3 selected from n , π c US, 5 to 6 members of the hetero atom of the right i, /, a single ring heteroaryl Γ Γ Γ — A or 3 nitrogen atoms 5 to 6 member heterocyclic group, or contain a single j heteroaryl Directly bonded to 5 to 6 M cyclofilament or heterocyclic soil, the heteroaryl or heterocyclic group contains 1, 2 or 3 nitrogen atoms, and the alkyl group, 4 alkyl group, cycloalkyl group, benzene a base, a heteroaryl group, a heterocyclic ring, or a double-filament-free or a thiophene-substituted substituent ς 原子 atom, a thiol group; a straight or branched chain crc6 alkyl group; a 5 to 6 membered monocyclic heteroaryl group having 1 or 2, 3 or 3 nitrogen atoms which is unsubstituted or substituted with one or more dentate atoms, which is unsubstituted or subjected to - or spicy a straight or branched chain crc3 alkyl group substituted with a C3_C7 heterocyclic ketone group containing 1, 2 or 3 nitrogen atoms which are unsubstituted or have one or more straight or branched chain C1 -C3 alkyl substituted; or

Rs represents a group of -0&3, wherein Rn represents a crc3 alkyl group which is unsubstituted or substituted with one or more stupid groups, or

Rs together with the nitrogen atom to which R5 is bonded, form a 5 to 7 membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and which is via a -C(〇MCH2)n-R10 group or _c( 〇)_(CH2)n_NRi〇Rii group substituted, wherein 11 is deuterium or 1' and R10 and Ru independently represent a hydrogen atom, a cyano group, a linear or branched chain CrC3 alkyl group, or a CrC4_alkyl group, • The limitation is that when „! is 〇, Re is not a _〇Ri3 group. In one embodiment, Rs represents a straight or branched chain CrC6 alkyl group, Ci-C4 dentate group, crc9 cycloalkyl group a phenyl group, a 5- to oxime monocyclic heteroaryl group containing 2 or 3 hetero atoms selected from the group consisting of ruthenium, osmium and S, containing i, 2 68 201130835 or 3 hetero atoms selected from n, oxime and S a 5- to 7-membered heterocyclic group containing 1, 2 or 3 nitrogen-substituted heterocycloalkyl ketone groups containing a stupid group directly bonded to 5 to 7 containing at least one hetero atom selected from the group consisting of ruthenium, S and N a bicyclic group of a heterocyclic group, or a bicyclic group containing a p-bonding group directly bonded to a C3-C7 cycloalkyl group, or R8 represents a -(CHJnOR group, wherein η is 0, 1 or 2 and R represents a linear chain Or a branched chain CrC6 alkyl group, or a CrC4 haloalkyl group; In particular, R8 may represent a 6-membered heterocyclic group containing 1, 2 or 3 hetero atoms selected from N, hydrazine and S; wherein the _alkyl group, cycloalkyl group, adamantyl group, stupid group, heteroaryl group a heterocyclic group, a heterocycloalkyl ketone group, and a bicyclic group are unsubstituted or substituted with one or more substituents selected from Ra; and the alkyl group is unsubstituted or substituted with one or more selected from Rb a base substitution wherein Ra and Rbw are as defined above. More preferably, when Rs is an alkyl group or a haloalkyl group, it is an unsubstituted alkyl group or a group; when & When the steel base is preferred or stupid, it is unsubstituted or via- or a plurality of selected from a functional atom, a two-chain or a ☆ branched CrC6 alkyl group, a CrC4 functional group or (CrC4 butterfly) Substituting a silky group; a heterocyclic group, which is not substituted (tetra) m... 8 (10) square reduction, wherein Ra is as defined above. One or more substituents selected from Ra are preferably, when It8 ^ is selected from a halogen atom, cyanide The substituent is substituted with or substituted with one or more substituents, and is also an integer of the dialkyl group, preferably 1. When the group is a base, m is from 1 to 3. Preferably, when R8 is a heteroaryl group. When it is contained - Or two nitrogen atoms 69 201130835 if it is a heteroaryl group. ° is more preferred than a pyridine group. Preferably, when R 8 is a heterogeneous, when or substituted by one or more ac tooth atoms. = when the hetero group is 'm is an integer from 1 to 3, preferably when it is a heterocyclic group, it preferably contains - or two is selected from a group. More preferably contains - or 5 of two nitrogen atoms Or a 6-membered heterocyclic ring. Difficult to 'heterocyclic group = exchange: it is said to be via a ring carbon atom and a base, the substituent on the earth may be present on any ring atom, but is preferably present on the nitrogen atom. Preferably, at least one substituent is present on the ring nitrogen atom. Most preferably, R8 represents a linear or branched chain CrC5 alkyl group, _(CrC5 alkyl MCrC2 alkoxy group), cyclohexyl group, adamantyl group, pyridyl group, 5,6,7,8-tetrahydroindenyl group, four a hydrogen donor or a donor group, the cyclohexyl group, adamantyl group, pyridyl group, tetrahydroquinolyl group, tetrahydropentanyl group, and anthracenyl group are unsubstituted or one or more selected from a halogen atom, a hydroxyl group, a straight or branched chain substituted with a substituent of an alkyl group or a CrC4 dentate alkyl group; or r8 is a piperidinyl group, a piperazinyl group, a pyrrolidinyl group or a pyrrolidinyl-2-one group, the piperidinyl group, a piperidine group a pyridyl group, a 0-Butyl group, and an n-butan-2-one group are unsubstituted or one or more selected from a linear or branched chain CrC3 alkyl group, a phenyl group, a carbene group, a trisal group, and a β group. Salivation, -8(0)2-((^2)0-,1^0 group, -(^0)-(012)0401^0 group, -C(〇HGH2)(mR10 group Substituted by a substituent of the '-QOHCHA-NRwRu group w(CrC4 alkyl)-CN group or -(CrC4 alkyl)-CXC^NRHjRn, wherein the phenyl group, π is a bite group, a triacetyl group, and a sputum Substituent unsubstituted or one or more selected from a halogen atom, a trans group, a cyano group, a linear or a branched bond 201130835

a CrC3 alkyl group, or a substituent of a crC4 south alkyl group, wherein _Rl1 represents a hydrogen atom, or a straight or branched chain crc4 alkyl group, and _RlG represents a hydrogen atom; a cyano group; a linear or branched chain crc5 Alkyl; CrC4 i ortho; crC5 anthracenyl; _(Ci_c4 alkyl) (Ci_c2 alkoxy); C^C: 6 cycloalkyl 'the cycloalkyl is unsubstituted or selected by one or more Substituted from a halogen atom, a hydroxyl group, a cyano group, a linear or branched chain Ci_C3 alkyl group, a _(Ci_C4 alkyl)-CN group or a substituent of a phenyl group; α is a pyridyl group, the acridinyl group is not substituted or Substituted by one or more substituents selected from a dentate atom or a cyano group; the phenyl group is unsubstituted or one or more selected from a halogen atom, a cyano group, a linear or branched chain C1-C3 Substituted with a substituent of an alkyl group or a crC4 hydroxyalkyl group; a pyrrolidinyl group which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; The thiol group is unsubstituted or substituted with one or more substituents selected from a functional atom, a hydroxyl group, or a linear or branched C1-C3 alkyl group; the porphyrin group is unsubstituted or Substituted by one or more substituents selected from a dentate atom, a cyano group, or a linear or branched Ci_c3 alkyl group; an imidazolyl group, _(CrC5 alkyl)-(phenyl), wherein the -(CrC5 alkane) The phenyl group of the group -(phenyl) is unsubstituted or substituted with one or more substituents selected from a halogen atom or a CrC2 alkoxy group; _(CrC5hydroxyalkyl phenyl)' wherein _( ^〇: 5-Hydroxyalkyl)-(phenyl)phenyl is unsubstituted or substituted with one or more substituents selected from a halogen atom or a CrC2 alkoxy group, 1-D-s-2,3-diindole The '1-non-2,3-disalyl group is unsubstituted or substituted with one or more straight or branched chain CrC3 alkyl groups; benzimidazolyl, the indenyl group is unsubstituted or Substituted by one or more linear or branched chain q_c3 alkyl; 10 alkyl; 2,2-dimercapto-1,3-dioxolyl I ^ 71 201130835 fluorenyl; fluorenyl; Hydrogen brigade; four salivation · _ remaining 2, war 3H) - two shouting. The base 'di-filament 4-saltyl group or in a particularly preferred embodiment, in the compound of formula (1), z is nr5; 戍Y is a nitrogen atom and X is X is a nitrogen atom and γ is a group _cr9 group- Cr9 ; heart table ^ atom, _ atom, cyano, linear or alkyl or CVQ cycloalkyl or tetracycline, 1 6 each independently represents a hydrogen atom, or a direct bond or a slit c, c 2.14 K represents a hydrogen atom, a south atom, a cyano group, or a CVQ group; the HV knife branch crc6 represents a hydrogen atom, a dentate atom, and a gas to a 6-membered monocyclic aryl group MU* C3_C4, 5, N, 0..., the heteroaryl contains 2 or 3 choices or vias - or more: sub-group: base! and heteroaryl unsubstituted bond (four) fiber or branch extract ^ represents -C(〇)〇Rl3 group, _C(0)_NRl3Ri4 group or 13 〇)R14 group', and Ri4 each independently represents a nitrogen atom, a bond or a branch bond C"C6 alkyl group , CrQ _ alkyl, CrC4 hydroxy alkane dioxin / 4 burnt oxygen county, C3-C7 cyclofilament, phenyl or 6-membered saturated N-containing heterocyclic ring; P 1 R4 represents no gas atom, 4 atom, cyano group , straight or branched chain Crc6 alkyl, or CH: 4 cycloalkyl; 72 201130835 I represents a hydrogen atom Straight or branched chain cc 院 仏 '仏 烧 ; ;; A alkyl, or Cl R6 and R7 each independently represents a hydrogen atom, a straight or branched bond substituted by cvc2 alkoxy groups CK: 3 ^ ^, R8 represents a linear or branched CVQ filament, a C C7 cycloalkyl group, an adamantyl group, a stupid group, a 5- to 6-member single containing a alkane 綦 12 or 3 hetero atoms selected from the group consisting of ruthenium, osmium and S a cycloheteroaryl group containing 2 or 3, a 5 to 7 membered heterocyclic group of a hetero atom of Ν'Ο and S containing a 2 or 3 IU subunit of crc7#Wei, a phenyl direct bond: containing a bicyclic group of at least one 5- to 7-membered heterocyclic group selected from the group consisting of a hetero atom of hydrazine, S, and N, or a bicyclic group having a group directly bonded to a CH:^f syl group, wherein the cycloalkyl group, Adamantyl, phenyl, heteroaryl, heterocyclyl, heterocycloalkyl ketone, and bicyclo are unsubstituted or substituted with one or more substituents selected from the group consisting of: a halogen atom; a hydroxyl group; a straight chain or a branch a chain Ci_C6 alkyl; a phenyl group which is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group; and contains 1, 2 or 3 selected from the group consisting of N, 0 and S. Atomic 5 to 6 a monocyclic heteroaryl group which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; -S(〇)2ri〇 group; -C(O)OR10; a C(O)-CH2-OR10 group; a -C(O)-(CH2)nO-(CH2)mR10 group; a -C(O)-(CH2)nO-(CH2)mO-R10 group; C(〇)-(CH2)n-R10; -NRwRu group; -QOXCiyn-NRioRu gene; -C(CVC4 alkyl-based VCXOHCHA-NRioRn group; -(CrC4 alkyl)-CN group or 73 201130835 -( Crc4 alkyl)-C(0)nr'r, a group 'where R, and is selected from a hydrogen atom and a straight or branched chain crc4 alkane the same or different or an integer from 1 to 5, and wherein m is ! η to the total number of soils, η is 〇Rio and Ru each independently represents a hydrogen atom, a cyano group, a medium chain CrQ alkyl 'CrC4 haloalkyl group, a CrC6 hydroxyalkyl group or a branched group '-( C丨-Q is calcined)-(phenyl), _c(〇)-(stupidyl), human 7 morning alkyl 3 or 4 heteroatoms selected from N, 0 and S 5 to j a group containing 9 or 1 member of the nitrogen atom, 9 to 1 member of the nitrogen atom, 1 to 2 or 3 nitrogen atoms, and 1 or 2 keto groups. 3 selected from n, 〇^s, early ring heterocycle = 6 membered heterocyclic group' or a bicyclic group containing a monocyclic (tetra)aryl or heteroaryl group directly to a 6-membered cyclohexene or heterocyclic group, said base or hetero The base contains 1, 2 or 3 heteroatoms selected from N, oxime and s, the cycloalkyl, strepto, heteroaryl, heterocyclyl and bicyclic groups are unsubstituted or selected by one or more Substituted from the following substituents: a hydroxyl atom; a hydroxy group; a cyano group; a linear or branched chain crc6 alkyl group; a crc4 haloalkyl group; a Cl<:4f alkyl group; a CrC4 alkoxy group; a phenyl group, the phenyl group 5 to 6 membered monocyclic rings containing 1, 2 or 3 nitrogen atoms, unsubstituted or substituted by one or a halogen atom An aryl group, which is unsubstituted or substituted with one or more straight or branched chain crC3 alkyl groups; or a C3-C7 heterocycloalkyl ketone group containing 1, 2 or 3 nitrogen atoms A heterocycloalkyl ketone group is unsubstituted or substituted with one or more of the alternate or branched chain CrC3 alkyl groups; or & represents an -ORn group, wherein R1S represents unsubstituted or substituted with - or a plurality of stupid groups (^-(:3 alkyl, or 74 201130835

Rs together with R5 and the nitrogen atom to which Rs is bonded together form a 5 to 7 membered saturated heterocyclic group which contains - or a two-slice atom as a hetero atom and which is subjected to a bite group, -C(〇HCH2)n-R1Q group Or ((9) 胤(胤)(10)" group substitution' wherein each η is 0 or 1, and wherein each Riq and % independently represents a hydrogen atom, a cyano group, a linear or branched chain Cl_c3 filament, or a Ci_C4 tooth-fired R9 represents hydrogen Atom, halogen atom, cyano group, straight or branched chain Ci_C4 alkyl group, CrC4 haloalkyl group, C3-C7 cycloalkyl group, containing !, 2, 3 or 2 4 selected from hetero atoms of N, Ο and S 5 to 6 noble monocyclic bases, or 5 to 7 membered heterocyclic groups containing 2 or 3 hetero atoms selected from N, fluorene and s, and their secret groups, cyclofilaments, heterofilaments, and impurities Take or pass through - or multiple selected from (iv) atom, cyano group, minus, linear or branched bond Crc6 alkyl group, -S(0)2R1 fluorene group, _c(〇)〇Rw group, -C(0) Substituted by a -(CH2)-Rh) group or a substituent of the -R10 group, wherein H 1 represents a hydrogen atom, a cyano group, or a linear or branched C1_C3 alkyl group, or 10 r9 represents -s(o) 2R13 group, _ORi3 group, c(〇)〇Ri3 group•NRnRH based IS or -CXO a group of XCHA-NR^4, wherein n is 1 and the cores 3 and RH each independently represent a hydrogen atom, a straight or branched chain c^ alkyl group, a KCVC4 alkyl alkoxy group or a _(CrC4 alkyl group containing 6 5 to 7 membered heterocyclic groups having one less hetero atom selected from 0, S and N. In the presence of two -CR9 adjacent groups, two _CR9 groups and their bonded carbon atoms Depending on the case, a 5- to 6-membered aryl group is formed in which the diaryl group is unsubstituted or substituted with one or more substituents selected from a halogen atom or a linear or sub-chain CrC4 alkyl group, 77 of which is 201130835 In the compound of formula (I), the limitation is that when m is 0, in another particularly preferred embodiment, m is 〇 or 1; Z is NR5; Group -CR9; a 1 von nitrogen atom and X is

Ri represents a hydrogen atom, a halogen atom, a cyano group,

The alkyl group, or the c3-c4 cyclofilament or the NRl3Ni4 smectic branched chain CVQ each independently represents a hydrogen atom, or a straight chain or a sub-, η, and Rm represents a nitrogen atom, «atoms, ^

An alkyl group, or a CVC4 cycloalkyl group; a linear or knife-branched chain, CrQ R3, which represents a gas atom, a dentate atom, or a 6-membered monocyclic aryl or heteroaryl group, said hetero-H4f-f group, 5 a hetero atom of n, hydrazine and s, said aryl group and m3: selected or via - or a plurality of selected from the unsubstituted R3 group -C(0)0R13 group, -C(〇)_NR13R丨4 group or -nr13c(o)r14 group 'wherein and Rl4 each independently represent a gas atom, a straight bond or a branched chain C1-C6 alkyl group, a CrC4 group, a C"c4 burnt group, a Crc4 burnt oxygen group a c3_C7 cyclodextrin, a stupid or a 6-membered saturated N-heterocyclyl ring; a c-generation =, r, an aryl group, or a straight chain or a branch R4 represents a gas atom, a halogen atom, a cyano group, a linear chain or Branched chain cvc6 alkyl, or C;j-C4 cycloalkyl. R5 is not a gas atom, a straight or branched chain Crc3 alkyl, or a Crc3 76 201130835 alkyl-c3-c7 cycloalkyl; or a straight chain or The branching stalks 6 and R·7 each independently represent a hydrogen atom Ci-C3 alkyl group; the heart represents a direct bond or a branched bond CrQ alkyl group, a CrC4 haloalkyl group, an alkoxy group, a q-C7 cycloalkyl group, an adamantyl group , stupid, containing 丨, 2 or 3 selected from N, 〇 and S 5 to 6 members of the monocyclic heteroaryl group: 5 to 7 membered heterocyclic groups containing 1, 2 or 3 hetero atoms selected from N, fluorene and S, or containing a phenyl group directly bonded to contain at least ― a bicyclic group of 5 to 7-membered heterocyclic groups selected from the hetero atom of hydrazine, s, and N, a ship's base, a south alkyl group, an alkoxy group, a cycloalkyl group, an adamantyl group, a stupid group, a heteroaryl group, The heterocyclic group and the double J group are unsubstituted or substituted by one or more substituents selected from the group consisting of: Α _ atom, hydroxy, straight or branched Crc6 alkyl, stupid, pyridyl, -s ( o) 2r1(), -c(0)0R1(), -qo^CHA-RiG, _NRi〇Ru group, -C(0)_(CH2)n_NRi〇Rn group, -(CrC4 alkyl)- a CN group or a -(CrC4 alkyl)-C(0)NR'R" group, wherein R, and R" are the same or different and are selected from a hydrogen atom and a straight or branched chain Ci_C4 alkyl; wherein n is 〇

Rio and Ru each independently represent a hydrogen atom, a cyano group, a linear or branched bond, a Cl_C6 alkyl group, a Cl% haloalkyl group, a CrC7 cycloalkyl 'phenyl group, containing i, 2 or 3 selected from N, oxime and s. 5 to 6 membered monocyclic heteroaryls of a hetero atom containing 5 to 6 membered heterocyclic groups of 2 or 3 nitrogen atoms, or containing a monocyclic C5-C6 aryl or heteroaryl group directly bonded to 5 to 6 members a heterocyclic or heterocyclic group of a cycloalkyl or heterocyclic group, wherein the heteroaryl or heterocyclic group contains 1, 2 or 3 nitrogen atoms & 77 201130835 . | bond as a bond C - C6 alkyl, more than 10% a halogen atom-substituted benzene 5 6-membered anthracene heteroaryl 'the bond or branched chain CrC3 alkyl group takes a C3-C7 hetero-cathyl ketone group, the alkyl group, the i-alkyl group, the ring-heat group, Benzene, heteroaryl, heterocyclic and bicyclic groups are unsubstituted or substituted by the following substituents. _ h ib 々Τ 在 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶 壶Cyano C1-C4 dentate; unsubstituted or via group; heteroaryl containing 1, 2 or 3 nitrogen atoms unsubstituted or substituted by one or more f; or containing 1, 2 or 3 Nitrogen atom I, heterocycloalkyl, shunt unsubstituted H or multiple straight chains or branches A C1-C3 deutero-substituted or R8 represents a -OR13 group, which represents a CVC3 alkyl group which is unsubstituted or substituted with one or more phenyl groups, or R8 together with the nitrogen atom to which Rs and R5 are bonded form 5 to a 7-membered saturated heterocyclic group containing one or two gas atoms as a hetero atom and which is substituted by a -(:(Ο)-((:Η2)η^10 group or a -CXOHCHA-NRwRu group, wherein η is 0 or 1 ' and Rio and Rii independently represent a hydrogen atom, a cyano group, a linear or branched chain CrQ alkyl group, or a CrC4 haloalkyl group; R9 represents a hydrogen atom 'halogen atom, a cyano group, a linear or branched chain CrC4 burnt Base, Q-C4 il thiol 'C3-C7 cycloalkyl' -Cj-Qj alkyl-C3-C7 cycloalkyl, 5- to 6-membered monocyclic heteroaryl containing 1, 2 or 3 nitrogen atoms, a 5- to 7-membered heterocyclic group containing 2 or 3 nitrogen atoms, the alkyl group, cycloalkyl group, heteroaryl group and heterocyclic group being unsubstituted or one or more selected from a cyano group or an -ORio group The substituent of the group is substituted by 'where Rio represents a straight or branched chain Crc3 alkyl group, or R9 represents a -S(0)2R!3 group, -C(〇)〇r13 group or _NRi3Ri4 group 78 201130835 group R13 and r14 each independently represent a hydrogen atom Or a straight or branched C1-C4 alkyl group, or in the presence of two -CR9 adjacent groups, the two -CR9 groups and the carbon atoms to which they are bonded form 5 to 9 members as appropriate The aryl group is unsubstituted or substituted with one or more substituents selected from a halogen atom or a linear or branched Ci-Q alkyl group, with the proviso that when m is 0, R8 is not _ 〇Ru group. In another particularly preferred embodiment, in the compound of formula (I), m is 0 or 1; Z is NR5; X is a nitrogen atom and γ is a group _CR9, or γ is a group -CR9;

Ri represents a hydrogen atom; represents a hydrogen atom; r3 represents a hydrogen atom 'dentate atom, a cyano group, a Ci_c4 dentate propyl group, an unsubstituted or a phenyl group substituted with a halogen atom or a plurality of halogen atoms, Or 3 5 to 6 membered monocyclic heteroaryls R3 selected from N and 〇: 丞 each having a hetero atom, or a hetero atom, a _C(0)0Rl3 group, a -NRnCW) group, wherein R 丨4 groups or methyl groups; and Rl4 independently represent a hydrogen atom or R4 represents a hydrogen atom; C4 ring-fired R5 represents a ruthenium atom, a methyl group, a taufanyl group or a -Ci-C3 alkyl-c, - 201130835 and R·7 each independently represents a hydrogen atom or a methyl group. R8 represents a straight or branched chain Crc6 alkyl group, a CrQ dentate group, a core c alkoxy group, a CrC7 ring-based adamantyl group, a phenyl group, and a phenyl group. 4 to 6 membered monocyclic heteroaryl groups selected from heteroatoms of N, 0 and S: 5 to 7 groups containing 2 or 3 hetero atoms selected from N, oxime and S or containing phenyl directly Bonded to a bicyclic group containing at least one 5- to 7-membered heterocyclic group selected from the group consisting of a hetero atom of hydrazine, s, and N, said alkyl group, a chiral alkyl group, an alkoxy group, a cycloalkyl group, an adamantyl group, Stupid, heteroaryl, heterocyclic And the bicyclic group is unsubstituted or one or more selected from the group consisting of a halogen atom, a hydroxyl group, a linear or branched chain CrQ alkyl group, a phenyl group, a pyridyl group, -s(o)2Rh), <(〇)〇&; , -c(0)_(CH2)n_Ri〇, _NRi〇R", -CCOHCHA-NRwR" group, _(crc4 alkyl)_CN group or -(CVC4 alkyl)-C(0)NR'R Substituting a substituent of a group wherein R, and R· are the same or different and are selected from a hydrogen atom and a straight or branched chain Ci_C4 alkyl, wherein n is 0 or 1, and

Rio and R" each independently represent a hydrogen atom, a cyano group, a linear or branched chain CrQ alkyl group 'CVQ haloalkyl group, a CrC7 cycloalkyl group, a phenyl group, containing 2, 3 or 3 selected from N, oxime and S. 5 to 6 membered monocyclic heteroaryls of a hetero atom, 5 to 6 membered heterocyclic groups containing 2 or 3 nitrogen atoms, or containing a single % CrCL aryl or heteroaryl group directly bonded to 5 to 6 members a heterocyclic or heterocyclic group of a cycloalkyl or heterocyclic group containing 1, 2 or 3 nitrogen atoms, an alkyl group, a 4 alkyl group, a cycloalkyl group, a phenyl group, a heteroaryl group a heterocyclic group and a bicyclic group which are unsubstituted or have a halogen atom, a trans group, or a plurality of substituents selected from the group consisting of: a cyano group; a linear or branched chain CrC6 alkyl group; 201130835

a CrCt fluorenyl group; a stupid group which is unsubstituted or substituted with a plurality of dentate atoms; a 5- to 6-membered monocyclic heteroaryl group having 1, 2 or 3 nitrogen atoms, the heteroaryl group being unsubstituted Or substituted by one or more linear or branched chain CrC3 alkyl groups; or a C3_C7 heterocycloalkyl ketone group containing 2 or 3 nitrogen sulfonium groups, which are unsubstituted or mediated by one or a plurality of straight or branched chain CrC3 alkyl groups, or a -OR13 group, wherein Rn represents a CrC3 alkyl group which is unsubstituted or substituted with one or more phenyl groups, or

Rs together with the nitrogen atom to which R5 and R5 are bonded form a 5- to 7-membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and which is via a -C(〇)-(CH2)n-R10 group Or -(^(^^(CH^n-NRioRu group substituted, wherein η is 〇 or 1, and r1q and independently represents a hydrogen atom, a cyano group, a straight bond or a branched bond C1-C3 alkyl group, or C1 -C4 _alkyl; R9 represents a hydrogen atom 'halogen atom, cyano' straight or branched chain crc4 alkyl group CVC7 cycloalkyl, 5 to 6 membered monocyclic heteroaryl group containing i, 2 or 3 nitrogen atoms a 5- to 7-membered heterocyclic group having 1, 2 or 3 nitrogen atoms, the alkyl, cycloalkyl, heteroaryl and heterocyclic groups being unsubstituted or selected from one or more selected from the group consisting of cyano or Substituent substitution of the OR10 group, wherein a straight or branched chain CrC3 alkyl group is represented, or 仏 represents a 4(0)2%3 group, a _c(9)0Rl3 group or a _NRi3Ri4 group, wherein R 3 and RM are each independently represented a hydrogen atom, or a straight or branched chain Ci-C4 alkyl group, or in the presence of two -CR9 adjacent groups, the two _Cr9 groups and the carbon atoms to which they are bonded form 5 to 6 as appropriate芳芳, the Fang 81 201130835 Substituting or substituting one or more substituents selected from the group consisting of a sulfonium atom or a straight bond or a branched bond crc4, the limitation is that when m is 〇, 'Re is not a 〇R13 group. In a preferred embodiment, the compound of the invention has the formula U"),

Formula (I',) wherein X is a nitrogen atom and γ is a _CR9 group, or γ is a nitrogen atom and X is a CR9 group; 尺3 is a hydrogen atom, a γ atom, a cyano group, a —C(〇)〇 R, a group, a C3-C4 cycloalkyl group, a pyridyl group, a pyrazolyl group or a phenyl group, which is unsubstituted or substituted by a halogen atom, 'there is a towel R, is a hydrogen material, or a linear or branched chain CrC4 Amorphous; '' R5 is a hydrogen atom, a methyl group, an ethyl group, a propyl group; or a ruthenium 5 together with a nitrogen atom bonded to R8 and Rs: 1,4-diazacycloheptane_ι_yl, The oxime, 4 • diazepanyl hydrazino group 82 201130835 is unsubstituted or substituted with a -c(o)ch2cn group, or a pyrrolidinyl group, which is unsubstituted or pyridyl Or a -C(0)N(CH2CH3)2 group substituted; R.6 and R7 each independently represent a hydrogen atom, or a straight or branched chain Crc3 alkyl group which is unsubstituted or substituted with a Ci-C2 alkoxy group; R8 together with the nitrogen atom to which R5 and R5 are bonded together form the 1,4-'-a gas-hetero-heptanyl group or σ-pyrrolidone; or Κ·8 is a chlorine atom, a straight bond or a branched Q-C5 alkane , -(Crc5 alkyl)-(crc2 alkoxy), cyclohexyl, diamond , phenyl, η than butyl, 5,6,7,8-tetrahydroindenyl, tetrahydropyranyl or 10 alkyl, said cyclohexyl, adamantyl, phenyl, pyridyl, tetrahydrogen The quinolyl group, the tetrahydropyranyl group, and the monoalkyl group are unsubstituted or one or more selected from the group consisting of a halogen atom, a hydroxyl group, a -CH2CN group, a linear or branched CrC3 alkyl group, or a CrC4 haloalkyl group. Substituent substitution; or r8 is piperidinyl, piperazinyl, pyrrolidinyl or pyrrolidin-2-one, the piperidinyl, piperazinyl, pyrrolidinyl and pyrrolidin-2-one are not Substituted or via one or more selected from the group consisting of a straight or branched chain CrC3 alkyl, phenyl, pyridyl, triazolyl, thiazolyl, -S(0)2-(CH2)nRi〇 group, _C(O) -(CH2)nOR10 group, -C(0)-(CH2)nR1() group, _C(0)_(CH2)n_N(Ri(})_(CH2)nRii group, -(CrC4 alkyl group a -CN group or a -(CrC4 alkyl)-C(O)NR10R„2 substituent substituted 'where η is 0 or 1, and wherein the phenyl, acridinyl, triazolyl and thiazolyl are not Substituted or substituted with one or more substituents selected from a functional atom, a hydroxyl group, a cyano group, a linear or branched chain CrC3 alkyl group, or a CrC4 tooth alkyl group, Wherein represents a hydrogen atom, or a linear or branched chain, and a decyl group, and 83 201130835 _R10 represents a hydrogen atom; a cyano group; a linear or a fraction == C5 嶋; - (CrC4 alkyl 2: 3 cyclization group) Unsubstituted or substituted by - or a plurality of (tetra) Ϊ Κ: chain or branched CL group, (d) functional burnt earth (丨4, aryl group)-CN group or phenyl substituent; The oxime is unsubstituted or substituted with a substituent selected from a halogen atom or an aryl group; the phenyl group is substituted or via- or a plurality selected from a dentate atom, a cyano group, a linear chain or Branched chain CrC3 filament, or Ci_C4 substituted alkyl group; the scale is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group; pyrimidinyl, the pyrimidine Substituent unsubstituted or substituted by one or more substituents selected from a functional atom, a hydroxyl group, or a linear or branched CrC3 alkyl group; 嗟α坐基' said 嗔σ sitting group is unsubstituted or via one or Substituting a plurality of substituents selected from a halogen atom, a cyano group, or a linear or branched chain crc3 alkyl group; an imidazolyl group, -(crc5 alkyl)-(phenyl), wherein the -(CrC5 alkyl group) a phenyl group of (phenyl) unsubstituted or substituted with one or more substituents selected from a dentate atom or a Ci_c2 alkoxy group; -(CrC5 hydroxyalkyl)-(phenyl), wherein said The phenyl group of (Ci-C5 hydroxyalkyl)-(phenyl) is unsubstituted or substituted with one or more substituents selected from a halogen atom or a CrC2 alkoxy group; 1_single 2,3-diπ a 丨-嗔-2,3-diindenyl group which is unsubstituted or substituted by one or more linear or branched bond C1-C3 alkyl groups; a benzimidazolyl group, the benzimidazolyl group is unsubstituted Or substituted by one or more linear or branched chain CrC3 alkyl; 1 〇 alkyl; 2,2-dimethyl-U-dioxolyl; imidazolyl; fluorenyl; tetrahydropyran A tetrazolyl group; a triazolyl group; a pyrazolyl group, a benzoinyl group or a pyrimidine-2,4(1H,3H): group. 84 201130835 R9 is a hydrogen atom; a halogen atom; a cyano group, a C1-C4 haloalkyl group, a straight or branched chain crc3 alkyl group; a CrC: 4 cycloalkyl group; D is a pyridyl group, and the pyridyl group is unsubstituted or Substituted by one or more substituents selected from carboxy or q-C3 alkoxy; triazolyl; tetrazolyl, unsubstituted or via one or more linear or branched CrC3 alkyl groups a pyrrolidinyl group, which is unsubstituted or substituted with one or more _c(〇)〇R'i3 groups; a substituent selected from a straight or branched chain crC3 alkyl group, or a -S(〇)2R, 13 group; morpholinyl; -S(〇)2r13 group; _〇r13 group; -C( 0) an ORR group; a NR13R14 group or a -C(〇HCH2)n-NR13R14 group; or when Y is a group R9, two adjacent R9 groups together with the carbon atom to which they are attached may form a benzene Ring; wherein η is 0 or 1 and each of R13 and R14 independently represents a hydrogen atom, a linear or branched chain CrC3 alkyl group, -(CrC3 alkyl MQ-Q alkoxy group), _(CrC3 alkyl group) Pyridyl); or -(CrC3 alkyl)-(morpholinyl); and R, 13 represents hydrogenogen Sub, or linear or branched chain CrC3 alkyl. In another particularly preferred embodiment, the compound of the invention has the formula (I,), 85 ? 8 201130835

R5 or γ is a nitrogen atom and wherein x is a nitrogen atom and Y is a -〇19 group X is a cr9 group; the rule 3 is a hydrogen atom, a dentate atom, an aryl group, c〇〇R, a group = a ke group , a mercapto group or a phenyl group, the phenyl group is unsubstituted, the flake R is a hydrogen atom, or a linear or branched bond is violent; - R3 is a hydrogen atom, a halogen atom, a cyano group, -C ( 〇)〇R, a group, a C3_C4 ring, a base, a fluorenyl group, the phenyl wire is substituted by a substituted or ^i atom, wherein R is a hydrogen hydrazine, or a straight or branched chain Ί^τ Μ · 4 & is a hydrogen atom, a fluorenyl group, an ethyl group, a -CHr cyclopropyl group, or R5 together with a nitrogen atom bonded to R8 and r5 to form a '4_dicycloheptane+ group, 1,4-diazepan-1(yl) is unsubstituted or substituted by _(:(〇)(:112(:1^ group; R·6 and R·7 each independently represent a hydrogen atom or Methyl; 86 201130835 R9 is a wind atom, a hydroxyl atom, or a fluorenyl group, an ethyl group, a pyrene, a pi-quinone or a pyridine, which is unsubstituted or substituted with a Ci_C2 alkoxy group, or when Y When the group is %, two adjacent R9 groups together with the carbon atom to which they are bonded a benzene ring may be formed; together with the nitrogen atom to which R5 and R5 are bonded, form the 1,4-diazepan-4-yl' or Rs to be a hydrogen atom, or a straight or branched chain Crc5 group, cyclohexyl group , adamantyl, pyranyl, brittle base, 1q alkyl, _(q_C5 alkyl)-phenyl, -(CrC5 alkyl)-cyclohexyl, alkyl)_(Ci_c2 alkoxy), -A -SO2-R', -A-A', -ALC(〇)]SiR,R,', -AL-CN, _A_C(0)-N(CrC2 alkyl)_L-CN, -AC(0)- NR'R,,, -AC(0)-A", -AC(0)-R",, -A-C02-R,,·Α·(:(0)heart A,,,, -AC( 0) a -L-CN or -AC(0)-L-〇-R' group, wherein r, and r" are the same or different and each represents a hydrogen atom, or a straight or branched chain leuco, and R" a non-linear or branched chain CrC5 alkyl, CrC2 haloalkyl or alkyl 'the cyclohexyl, adamantyl, piperanyl, piperidinyl and 1-decyl unsubstituted or dentate atom, or a hydroxy, straight or branched chain CrC2 alkyl or a crc2 decyl group, and wherein L is a linear or branched chain CrC5 alkyl, A is piperidinyl or pyrrolidinyl, unsubstituted or Ci_C2 alkane Base , ..., A' is phenyl or a pyridine group \ which is unsubstituted or substituted with hydrazine or two functional atom or a CN group, A" is pyrrolidinyl, pyridyl, pyrazolyl or cyclopropyl, The pyrrole bite group is replaced by two 87 201130835 halogen atoms or cyano groups, and A'" is an imidazolyl group. Specific individual compounds of the invention comprise: 3-(4-{[(lS)-l-phenethyl]amino}pyrimidin-2-yl)imidazo[1,2-a]acridin-6-indolecarbonitrile 3-(4-{[(lR)-l-phenethyl]amino}pyrimidin-2-yl)imidazo[l,2-a]pyridine-6-indolecarbonitrile; 3-[4-(benzene Methylaminopyrimidin-2-yl]imidazo[1,2-β]pyridine-6-indolecarbonitrile; 3-(4-{[(15>2-decyloxy-1-methylethyl)amine 5-pyrimidin-2-yl)imidazo[1,2-α]pyridine-6-indolecarbonitrile; 3-{4-[(cyclohexyl)amino]pyrimidin-2-yl}imidazo[1, 2-fl]acridine-6-carbonitrile; 3-{4-[(2-methoxyethyl)amino]pyrimidin-2-yl}imidazo[l,2-fl]pyridine-6-meth ; 3_{4-[(1-adamantyl)amino]pyrimidin-2-yl}imidazo[1,2]pyridin-6-carbonitrile; 3-{4-[(2,2-di) Methylpropyl)amino]pyrimidin-2-yl}imidazo[1,2-α]acridin-6-carbonitrile; 3-{5-bromo-4-[(2,2-diphenyl) Amino]pyrimidin-2-yl}imidazo[1,2- <3]α ratio π定-6-曱 guess, 3-{4-[(2,2-dimercaptopropyl)amino]-5-Brigade aqin-+!-base-mouth-2-yl }·11 m 0 sit and [l,2-a]0 than bite-6-indene nitrile; 3-[4-[(2,2-dipropylpropyl)amino]-5-(2-methoxy Acridine-4-yl)pyrimidin-2-yl]1^m. Sit and [l,2-a]n ratio α定-6-甲猜, 88 201130835 3-[4-[(2,2-Dimercaptopropyl)amino]-5-(2-sideoxy- 1,2-dihydroacridin-4-yl) mouth bite-2-yl] mouth rice 〇 sit and [l,2-a]ntt»a -6-曱 guess, 3-{4-[(2 , 2-dimercaptopropyl)amino] is more than 唆-3-yl-n-butyl-2-yl}-mouth saliva[1,2-a]0 than bite-6-carbonitrile; 3-{4-[ (3-fluorobenzyl)amino]pyrimidin-2-yl}imidazo[l,2-a]acridin-6-carbonitrile; 3-{4-[(4-fluorophenylhydrazino)amino Pyrimidin-2-yl}imidazo[1,2 is acridine-6-carbonitrile; 3-{4-[(2-methylphenylhydrazino)amino]pyrimidin-2-yl}imidazo[1 , 2^] 吼 bit-6-A guess, 2-({[2-(6-cyanoimidazo[1,2-ciridine-3-yl)pyrimidin-4-yl]amino} methyl Piperidine-1-decanoic acid tert-butyl ester; 3-(4-{[(1-ethyl-branyl)-2-yl)methyl]amino))唆-2-yl) σ米σ And [1,2-β]π ratio bite-6-method, 3-[4-(tetrahydro-2/ί-pyran-4-ylamino)pyrimidin-2-yl]imidazo[1, 2-α] ntt <a -6-A guess, 3-(4-(8-fluoro-1-decan-4-ylamino)pyrimidin-2-yl)imidazo[l,2-a] 吼-6-A Guess, 3-[4-(cyclohexylamino)pyrimidin-2-yl]imidazo[1,2-α]pyridine-6-carbonitrile; 3-{4-[(trans-4-hydroxycyclohexyl) Amino]pyrimidin-2-yl}imidazo[1,2-α] 0 is more than 唆-6-曱, 3-{4-[(5-hydroxy-2-adamantyl)amino]pyrimidine-2 -yl}imidazo[1,2-α]acridin-6-indolecarbonitrile; 3-{4-[(5-hydroxy-2-adamantyl)amino]pyrimidin-2-yl}imidazolium 89 201130835 [1,2-ίζ]σΛσ定-6-曱 guess, 2_{4_[(2,2-dipropylpropyl)amino]啥嗤琳_2_基}咪嗤[U a] 0 than bite -6-phthalonitrile; 3_{4·[phenylhydrazyl (fluorenyl)amine]-biting-; 2-yl}-salt and [l,2_a]n-pyridyl-6-carbonitrile; 3-( 4_{[(15>1-Phenylethyl)amine} mouth bite_2_base) 0 m 0 sit and [^-rushed than pyridine-6-decanoic acid; 2- (6-fluoroimidazo[1, 2-a]pyridin-3-yl)-Aq(1) phenylethyl]pyridin-4-amine, trans-4-{[2-(6-fluoroimipirin[1,2- <3] bite-3_yl) spray 11 _4_yl]amino} cyclohexanol; 3-(4-{[(ZS,75>5-hydroxy_2.adamantyl]amine group }哺啶_2基)imidazo[1,2- <3]pyridine-6-phthalonitrile; 7V-(2,2-dimethylpropyl)-2-0 m a sitting and [1,2-α]° ratio biting-3-ylated bite-4- Amine; ^(2,2--propyl)_2_ 米米σ sita[1,2-iz]ntb^-3-yl-6-17 ratio bite-3. pyrimidine-4-amine; 3- (6_{[(15>1-Phenylethyl)amino}pyridazin-2-yl)isoxazo[1,2-division bite-6-曱 guess; 3-{6-[(cyclohexanide) Amino]naminopyrazine-2-ylidene carbonitrile; I. 6-(6-fluoroimidazo[ΐ,2-α]acridin-3-yl )-Λ4(15>1-phenethyl]0-pyridin-2-amine;6-(6•chloroimidazo[ΐ,2-α]acridin-3-yl)-#_[(15>1 -Phenylethyl]0 is more specific than 201130835; (6)-6_(imidazo[1,2-a] °pyridin-3-yl)-N-(1-phenylethyl)pyridazine-2- Amine; 6-(6-cyclopropylimidazo[1,2-fl] ° pyridine-3-yl)--((1 phenylethyl)pyrazin-2-amine; #-[(15 )-1-phenethyl]-6-(6-0 is more than -3--3-imidol[1,2-α]pyrene than -3-yl)pyrazin-2-amine; iV-[( lS)_l-phenethyl]-6-(6-° ratio biting>4-based miso and [1,2- <j] mouth ratio -3-yl)pyrazin-2-amine; Λ4(11-phenethyl)-6-[6-(1//-°bazin-4-yl)imidazo[1, 2-4 π ratio lean-3-yl] ° 嘻-2-amine; Α4(15>1-phenethyl]-6-(6-phenylimidazo[1,2-α]η-pyridinyl- 3-yl)pyrazin-2-amine; 6-[6-(4-fluorophenyl)isoxazo[1,2-decaderidin-3-yl]-A4(1*S)-1-benzene Ethyl]ntb嘻-2-amine; 3-(4-{[(3i〇-l-(ethanesulfonyl)piperidin-3-yl]amino}pyrimidin-2-yl) imidazo[1, 2-α]pyridine-6-carbonitrile; 3-(4·{[(3Λ)-1-(isopropyl)-branched-3-yl]amino}}}}) [1,2-α]pyridine-6-indene nitrile; 3-(4-{[(3 and)-1-(cyanoethenyl)-derived _3·yl]amino}}}} Imidazo[1,2-4pyridine-6-carbonitrile; 3-(4-{[(3i?)-l-propionylpiperidine-3-yl]amino}pyrimidin-2-yl) Isozo[1j-a]'1 ratio bite-6-carbonitrile; 3-[4-({(3 cyano-1-[(1-cyanocyclopropyl))yl]piperidinyl) ) Amino) 201130835 Shouting bit-2-yl] σ米0 sitting and [1,2-ίζ]π than setting -6-曱 guess, 3-(4-{[(3幻-1-(曱氧Benzyl)piperidin-3-yl]amino}pyrimidin-2-yl) ρm σ sit and [1,2-ί3]π ratio 0 -6-曱 guess, 3-(4-{[ (3i?)-l-(3-hydroxy-3- Butyl acyl) piperidin-3-yl] amino} matter bite-2-yl) imidazole and laugh [1,2- <3]0 ratio bite-6-indene nitrile; 3-(4-{[(3Phanto-1-(3,3-dimethylbutylidene)piperidin-3-yl]amino}pyrimidin-2- Imidazo[l,2-fl]acridin-6-carbonitrile; 3-(4-{[(3 and)-1-(1//-imidazo-1-4-ylethyl)pipech Acridine-3-yl]amino}Nursing-2-yl) 0-seat and [l,2-fl]n ratio π--6-A guess, 3-[4-({(3幻-1- [(5-Cyanoacridin-2-yl)carbonyl]piperidin-3-yl}amino) ♦ 咬-2-yl] 0 m saliva [1,2-ύ?] π ratio ° -6 - A guess, 3-(4-{[(37?)-1 -(3,3,3-trifluoropropyl)piperidin-3-yl]amino}-pyridin-2-yl rice 0 sit And [l,2-fl]n is more than -6--6-A guess, (3 and)-3-{[2-(6-cyanoimidazo[1,2-α]acridin-3-yl) Pyrimidin-4-yl]amino}-#, dimethylenepiperidin-1-indenylamine; 3-{4-[((37〇-1-{[(2\45)-2-cyano) -4-Fluoropyridin-1-yl]carbonyl} B. -3-yl) Amino] Mouth bite ^- base} 11 m π sit and [1,2-β]αΐ^^-6-曱 guess , 3-(4-{[(3i?)-l-(5-cyanoacridin-2-yl)piperidin-3-yl]amino}pyrimidin-2-yl)imidazo[1,2- α]pyridine-6-carbonitrile; 3-(4-{[(3phan-1-(4-cyano-2-fluorophenyl)piperidin-3-yl]amino}pyrimidin-2-yl) σ米0 sits and [1,2-α]0 is more than bite-6-carbonitrile; , 3-{4-[[(37?)-1-(cyano)醯))piperidin-3-yl](methyl)amino]pyrimidin-2-yl j·11 m α sit and [1,2-ίζ]π than bite-6-曱 guess, 3-(4 -{[(35>1-(cyanoethyl)piperidin-3-yl]amino}pyrimidin-2-yl) 92 201130835 Miso[1,2-α]β is more than 唆-6-曱Nitrile; cis-3-(4-{1·(cyanoethenyl)_4-methylpiperidine-3-yl]aminopyrimidin-2-yl-methane 0 sits and [1,2-α] π ratio bite 6-carbonitrile; cis-3-(4··^·(ethanesulfonylindole-mercaptopiperidin-3-yl)amino}carcinoma-2-yl)imidazo[1, 2·α]ηpyridin-6-indene nitrile; 3_{4_[[1-(ethylsulfonyl)-4(methylpiperidinyl)-3-yl](methyl)amino]pyrimidin-2-yl }1*米唾和[1,2-α]πϋ°^>6-phthalonitrile; 3-((3i?)-3-{[2-(6-fluoroimidazo[i,2-external ratio] Acridine_3_yl) carcinoma 嗔_4_yl]amino}piperidin-1-yl)-3-oxo-propanonitrile; (8)-1-(3-(2_(6-azamidazo[i,2,2) - φ pyridine _3_ yl) pyrimidine _4 · ylamino) brigade bit -1-yl) Cyclopropanil phthalonitrile; 2_(6_Fluorozomib[1,2-carbidin-3 -基)善[(from) small (3,3,3-trifluoropropanyl) 唆-3-yl] mouth bite-4 amine; 2_(6_ fluoroimidazo[1,2_β]pyridine _3_ group )--[(3i?)-l-(l/f-pyrazol-4-yl-yl)3 bottom--3-yl]- _4_amine; 37?) good (cyanomethyl)·3_{[2_(6·Fluoromazole[1,2-oxicilidine·3-yl) cancer bite·4·yl]amine} Oleamine; 2-((3/〇-3-{[2-(6-fluoroimidazo[1,2-α]acridin-3-yl)pyrimidin-4-yl]amino}piperidine -1-yl)-2·methylpropanamide; 2-(6-fluoroimidazolium π than 唆_3_yl) methyl-indole 4 (3 and) small (3,3,3-trifluoropropene) (8)-3-(3-((2-(6-fluoroimidazo[i,2-a]acridin-3-yl)pyrimidin-4-yl) (methyl)amino)nidanyl-1-yl)_3_sideoxypropionitrile; (7?)-1-(3-((2-(6-fluoroimidazo[i,2-a]) ° than bite-3 -yl)pyridin-4-93 201130835 base X methyl)amino)α bottom sigma--1-yl) cyclopropanone carbonitrile; 3 -((3 and)_3· ·{ Ethyl [2·(6_Fluorine). Mizozo[1,2-β] π-pyridin-3-yl)pyrimidin-4-yl]amino}0 hen-1-yl)_3_sideoxypropionitrile; TV-ethyl-2- (6-fluoroimidazolium acridine_3_yl) [(from)-1-(3,3,3-trifluoropropenyl) brigade bite _3 base] pyrimidine-4-amine; 3-(( 3 幻_3-{(cyclopropylmethyl)[2_(6-fluoro 0-mazole and tl, 2_exopyridinyl·3·yl) Painful ice base] Amino group _3·Sideoxypropionitrile; #·(cyclopropanyl)-2-(6-fluoroimidazo[ι,2-β]pyridin-3-yl)good [(3 and)-1-(3) , 3,3·trifluoropropyl hydrazide), bite _3_yl] mouth bite _4·amine; 3-((3 and)-3_{[5-fluoro-2·(6·fluoroimidazolium acridine 3-yl)pyrimidin-4-yl]amino}Benyl-1-yl)-3-oxo-propanonitrile; 5-fluoro-2-(6-fluoroimidazo[Ww]pyridylpyridyl)- #-[(3/?)-1-(3,3,3·trifluoropropyl) sent bite _3_ base] 唆4_amine; 3-((3i?)-3-{[ 2-(6-fluoroimidazo[ι,2_β]π pyridine·3_yl)_5_methylpyrimidin-4-yl]amino}Ben-1-yl)-3-sided oxypropionitrile; 2 - (6-fluoroimidazo[ΐ,2·α]pyridine-3-yl)-5-methyl-7V-[(3 and)-1-(3,3,3·trifluoropropenyl) Biting-]·yl]♦-4-amine; 3-((3/?)-3-{[2-(6-fluoroimidazo[ι,2_α]α-pyridyl_3_yl)pyrimidine_4_yl ] } a 比 -1- -1- yl)-3- oxo-propanoid; 3-{4-[4-(cyanoethenyl)-i,4-diazepane-丨-yl Pyrimidine_2_yl}imidazo[l,2-a]pyridine-6·phthalonitrile; 3-((3Λ)-3-{[5-chloro-2-(6-fluoroimidazo[1,2 -β]acridin-3-yl)pyrimidin-4-yl]amino}pyrene-1-yl)·3-sideoxypropionitrile; 3·((3Λ)-3-{[2-( 6-1 imidazo[ι,2_冲比 bit_3_基), bite-4-yl] 94 201130835 Amino}π辰咬-1-yl)-2,2-dimercaptopropion, 2- ((3/^)-3- {[2-(6-gas σ米° sit and [1,2· <3] 0 than -3-yl), -4-yl]amino}piperidin-1-yl)acetamide; (S)-2-(6-qi ρ mβ sits and [1 , 2-a] ° ratio -3-yl)-N~(l -(5-gas π ratio bit-2_yl)ethyl)pyrimidine-4-amine; 2-(6-fluoroimidazo[l , 2-a] acridine-3-yl)-indole-10-pyridyl-2-ylmethyl)pyridin-4-amine, (S)-2-(6-fluoroimidazo[1,2-a] Acridine-3-yl)-N-(1-(4-fluorophenyl)butyl)pyrimidine_4_amine; (R) -3-(2-(6-gas °m σ sit and [1, 2-a]π is more than 唆-3-yl) Pain-4-ylamino)-1-propyl^Biluo 定-2-嗣, 6-gas-3-(4-(2-(' ° 唆-2-yl) '1 洛 -1--1-yl) mouth bite-2-yl) '3 m 11 sit and [l,2-a]0 than mouth; (S) -N,N -diethyl-1-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-yl)pyrrolidin-2-ylamine; (R)-N , N-diethyl-1-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-yl)pyrrolidin-2-ylamine; 2-( (lr, 4r)-4-(2-(6-gas 11 m salido[1,2-a]B is more than -3-yl) aceton-4-ylamino)cyclohexyl)acetonitrile; (R )-2-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino) brigade bite-1-based base) , (R)-4,4,4-Trifluoro-1 -(3-(2-(6-fluoroimidazole) [1,2-a] acridine-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)butan-1-one; ((R)-3-(2-(6-gas 57) Rice α sits and [1,2-a] ntba -3-yl)carban-4-ylamino) 95 201130835 piperidin-1-yl)((lR,2R)-2-phenylcyclopropyl Anthrone; (R)-1 -((R)-3-(2-(6-fluoroimidazo[1,2-ap)pyridin-3-yl)pyrimidin-4-ylamino) _1_yl)_2-carbyl-3,3-dimercaptobutan-1-indole, (R)-2-cyclopentyl-1-(3-(2-(6-fluoroimidazo[1, 2-dipyridin-3-yl)pyrimidin-4-ylamino)Nanthene-1-yl)acetamidine, (R)-l-(2-(3-(2-(6-fluoroimidazolyl) [l,2-a]Acridine-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)-2-oxoethyl)-5-methylpyrimidine-2,4 (1H , 3H)-dione; (R)-l-(3-(2-(6- 乱°米β sits and [l,2-a]n ratio bite 3-yl) pain ° -4- base Amino)piperidin-1-yl)-2-(1Η-1,2,4-triazol-1-yl)ethanone; (R)-(3-(2-(6-气1^α坐) And [1,2-a] ° is more than -3 -yl), and the amino group is a group of (1 - 2-ylamino)piperidin-1-yl)(1-indolylcyclohexyl)fluorenone; Fluorocyclopropyl)((尺)-3-(2-(6-fluoroimidazo[1,2-0-pyridin-3-yl)-inden-4-ylamino) α-chen-1-yl ) hyperthyroidism, ((R)-3-(2-(6-qi-negative β sitting and [1,2-a] ^^-3-yl) σ定-4-ylamino)piperidin-1-yl)((lR,2S)-2-hydroxycyclopentyl)methanone; (R)-l-(3-(2-(6-fluoroimidazole) And [l,2-a] acridine-3-yl)pyrimidin-4-ylamino) brigade-1-yl)-2-(1Η-α is -1--1-yl) B@同, ( R)-cyclohexyl (3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)anthone; R)-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)(4-methyl- 1,2,3-thiadiazol-5-yl)anthone; (R)-l-(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidine 4--4-aminoamino)piperidin-1-yl)-2-(4-(hydroxymethyl)phenyl)ethanone; 96 201130835 (S)-1 -((R)-3-(2-( 6-fluoro-salt and [丨, 2_a] β than bite _3_ base) squeezing _4-ylamino) Ninjabita-1-yl)-3~phenyl butyl 丨,; (8)-l-(( R)-3-(2-(6-fluoroimidazo[丨,2_a],pyridyl)pyridylamino)piperidin-1-yl)-3-indolyl·y-one; R) 1 ((2 (6 odor sits and [i, 2_a]n than bite-3-yl) mouth bite 4-ylamino) brigade-1-yl)-3-(4-methoxybenzene (R)-(5-fluoro-2,6-dihydroxypyrimidin-4-yl)(3_(2_(6-fluoroimidazo[l,2-a]acridin-3-yl) ) pyridine _4_ylamine ) ketone small base) ketone; (R)_2-(3_gasphenyl)_1 _((R)-3 -(2-(6-fluoroimidazo[1,2-a] η-pyridin-3 -()-pyrimidine-4-ylamino)π辰咬_ι_基)_2_hydroxyethyl ketone; (R)-(3-(2-(6-fluoroimidazo[丨,2] 3_yl)pyrimidine_4.ylamino)piperidin-1·yl)(pyrimidin-5-yl)methyl-; WW'fluorozimidopyridine 3yl)pyridyl 4 piperidin-1-yl)( 1-(trifluoromethyl)cyclobutyl)methanone; (R): (H2-(6|m salido D, 2 external ratio bite _3 base) icylamino) piperidin-1-yl (1-hydroxycyclopropyl)methanone; 派二 == (4) sulfosyl--ylamino) yl) 丨 基 基 傅 傅 傅 傅 傅 傅 疋 疋 基 基 基 基 基 基 基 基 基Base)] Na 3 · (¥ 氟 ° 米顿 12♦ than bite each base) bite _4_ ylamino) pie bite-1-yl group by methyl ethyl ketone; 97 201130835 (8)-1-(3-(2 (6•Fluoroimidazo[^bipyridinyl-3-yl)pyrimidin-4-ylamino)nidanyl-1-yl)_2-(methylamino)ethanone; (8)-1-(3-(2- (6-fluoroimidazo[丨,^]pyridine-3-yl)pyrimidinylamino)pyridin-1-yl)_2-fluorenylmethoxyethoxy)ethanone; (R)-l-( 3-(2-(6-fluoroimidazolyl)pyrimidinylpyrimidinyl-4-ylamino)α-bottom-1-yl)-; 2-(2-methylindole_4_yl)- ; (8)-(3-(2_(6 Flumiquinone [丨义小比pyridine_3_基)♦定_4·ylamino) 派-l-yl) (tetrahydro·2Η-〇辰喃_4_yl)methanone; (8)- L-(3-〇(6-fluoroimidazo[i,2_a]pyridine·3·yl)pyrimidine _4_ylamino)0 bottom-l-yl)-2-(2-methyl-1Η- Benzo[d] mouth rice "sit and ΐ·ι_基) ethyl ketone; 10 alkyl-3-yl ((R)-3-(2-(6-fluoro-spiro-[i,2_a]D ratio bite _3_基) shoutin-4-ylamino) ketone-1-yl) formazan; (R)-N-(2-(3-(2-(6·fluoroimidazo[1,2- a]pyridine-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)_2_sideoxyethyl)-indole-mercaptophenylamine; (R)-2-(3- gas phenoxy (1)(1-(2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)) oxime-4-ylamino)pyr (R)-l-(3-(2-(6-fluoroimidazo[1,2-&]°) acetyl-3-ylamino)pyrylene-4-ylamino) -2,2-bis(methyl)butanone; (R)-l-(3-(2-(6-fluoroimidazo[1,2-&]°) Pyrimidine-4-ylamino) ° chen-1-yl)-2-(2H-tetrasyl-5-yl)ethanone; 1^-(1-(111_1,'2,4-diindole_ 3-base) brigade bite _3_base)_2-(6-fluoro '1 m β sita and [l,2-a]D than _3_ base) cancer bite-4-amine; (R)-2 -(3-(2-(6-fluoroimidazo[i][i , 2-a] acridine-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)thiazole-5-indolecarbonitrile; 98 201130835 (R) -1 -((R)-3-( 2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)-2,3-dihydroxypropan-1-one; (S) -l-((R)-3-(2-(6-gas °mα sits and [l,2-a]π is more than -3-yl) ♦Bite-4_ylamino)1^ 11定_1_基)_2,3-二事为基丙-1-酉同, (R) -3-(3-(2-(6-fluoroimidazo[l,2-a]acridine- 3-yl)-5-mercaptopyrimidin-4-ylamino)ntb-l-yl-1-yl)-3-oxo-propion, (S)-2-(6-fluoroimidazo[1,2 -a] acridine-3-yl)-N-(l-(5-fluoroacridin-2-yl)ethyl)_5-methyl pain bite-4-amine, 2-(6-fluoroimidazo[ 1,2-a] acridine-3-yl)-N4-((5-fluoro"pyridin-2-yl)methyl)pyrimidine-4,5-diamine; 2-(6-fluoroimidazo[ l,2-a]pyridin-3-yl)-indole 4-(5,6,7,8-tetrahydroquinolin-5-yl) shouting-4,5-diamine; (R) -2-( 6-air mouth rice 0 sitting and [l,2-a]π than biting-3-yl)-Ν4-(3-mercaptobutyl-2-yl)pyrimidine-4,5-diamine; 2-(6-fluoro Imidazo[l,2-a]acridin-3-yl)-N4-(l-methoxypropan-2-yl)pyrimidine-4,5-diamine; 2-((lr,4r)-4 -(5-Amino-2-(6-fluoroimidazo[l,2-a]»pyridin-3-yl)pyrimidine-4- Amino)cyclohexyl)acetonitrile; (lr,4r)-4-(5-amino-2-(6-a gas 1π sitting and [1,2-a]D than -3-yl) carcinoma 唆-4 -ylamino)-1-methyl 哀 己 hexanol, ·- 2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-indole 4-( 1 -(5,-fluoro "Bidi-2-yl)-2-methoxyethyl) carcinoma-4,5-diamine; (S)-2-(6-fluoro-sigma-[1,2-a] ntb bite- 3-yl)-4-(1 -(5-1 ° ratio bit_2_yl)ethylamino)pyrimidine-5-carboxylic acid; 99 201130835 (S)_2-(6- defeat °米唾和[1,2 -a] ° ratio -3-yl)-4-( 1 -(5-gas 11 σ σ _2 yl) ethylamine) mouth bite-5-carbamide; ($)-2- (6-Fluor '3 m'» sits and [1,2-&]11 is more than '1-3-yl)-4-((1-(5-fluoro)-bit-2-yl)ethyl ) (methyl)amino) mouth bite _5_ formic acid; 2-(6-fluoro miso and [l,2-a]oit^-3-yl)-4-(0-bito-3-ylindole Amino) shouting 5-carboxylic acid; 2-(6-fluoroimidazo[1,2-micropyridin-3-yl)-4-(acridin-3-ylmethylamino)pyrimidine-5- Guanidine; 2-(6-fluoroimidazo[l,2-a:K)-3-yl)-4-((5-fluoroacridin-2-yl)methylamino)pyrimidine-5-carboxylic acid; 2-(6-fluoroimidazo[l,2-a;hbpyridin-3-yl)-4-((5-fluoroacridin-2-yl)nonylamino)pyrimidine-5-carboxamide; S)-2-(6· Flumimidazo[1,2-micropyridin-3-yl)-4-(1-(4-fluorophenyl)butylamino)pyrimidine-5-decanoic acid; (S)-2-(6-fluoro Imidazo[1,2-a]acridin-3-yl)-4-(1-(4-fluorophenyl)butylamino)pyrimidine-5-decylamine; 4-((lr,4r)- 4-(cyanoindolyl)cyclohexylamino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-5-carboxylic acid; 4-(( 1 r,4r) 4-(cyanomethyl)cyclohexylamino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-5-decylamine; ((R)-2 ,2-dimethyl-1,3-dioxol-4-yl)((R)_3-(2-(6-fluoro 0 m α sita[l,2-a]n ratio Benzyl-3-yl)-5-methylsodium-4-ylamino)piperidin-1-yl)anthone; (R)-l-((R)-3-(2-(6-fluoro) Mouth squat and [l,2-a]n than bite-3-yl)-5-mercapto 100 201130835 ♦ 咬-4-ylamino) sent bit-1-yl)-2,3-di Propion-1-yl, (R)-3-(3-(5-amino-2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamine Base) brigade bite-1-yl)-3-side gas-based cyan, (R)-3-(3-(5-i-propan-2-(6-fluoro 0 m α sitting and [l, 2 -a]a is more than -3-yl) ♦ bit -4-ylamino) brigade-1-yl)-3-sided oxypropyl, (R)-4-(l-(2-cyanide) Benzyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[l,2-a] n is more than -3-yl) squirting -5. 曱 guess, (R)-3-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-5 -(曱sulfonyl) oxime-4-ylamino) brigade-1-yl)-3-oxo-propion, (R)-4-(l-(2-cyanoethyl) Piperidin-3-ylamino)-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidine-5-decanoic acid ethyl ester; (R)_4-(l-(2 -1 base ethyl) π chen-3-ylamino)-2-(6-p-p-pyrazino[1,2-a]pyridin-3-yl)pyrimidine-5-decanoic acid; 4-(1-(2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-5 -carbamamine; (R)-3-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-5-decyloxypyrimidine-4-yl) Amino) brigade-1-yl)-3-oxo-propanoid; (R)-3-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl) )-6-(1Η-1,2,4-diηη_1_yl) mouth π定-4-ylamino) 底 bottom bit-1-yl)-3-lateral oxypropyl guess; (R )-3-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-6-(4-methylpiperazin-1-yl-4-amine (R)-3-(3-(2-(6- oxazolo[1,2-a]acridin-3-yl) )-6-(piperazine-1-yl)-mouth -4-ylamino)B-butyl-1-yl)-3-oxo-propanoid, (R)-3-(3-(2- (6-1 meters And [1,2-a] acridine-3-yl)-6-(4-(sulfonium 101 201130835 fluorenyl)piperazin-1-yl)pyrimidinyl)pyridinyl-1_yl)_3 · Sideoxypropionitrile; (R)-3-(3_(2-(6-fluoroimidazo[1,2_a]acridin-3-yl)-6-(N-morpholinyl)pyrimidin-4-yl Amino)piperidin-1-yl)_3_sideoxypropionitrile; (8)-3-(3-(6-(dimethylamino)-2-(6-fluoroimidazo[l,2-a] Pyridin-3-yl)pyrimidin-4-ylamino)nidanyl-1-yl)-3-oxo-propanonitrile; (R)-3-(3-(2_(6-fluoroisoxazole[1] , 2-a] 吼-3-yl) _6·(2-(indolyl-morpholinyl)ethylamino) hydrazide ylamino)pyridin-1-yl)-3-oxopropanenitrile ; (R) _3_(3_(2_(6-fluoro® methane hydrazide [i,2-a]° than bite base)-6-(2-oxoethylamino) aceto-4-ylamino) Pieces-1-yl)_3· pendant oxypropionitrile; (S) -l-(6-((R)-l-(2-cyanoethyl)- _3_ylamino)- 2-(6- odor β sits and [l,2-a]n is more than α--3-yl) -4-yl) "»Bilo bite-2-carboxylic acid; (R)-3-(3 -(2-(6 fluoro σ 嗤 嗤 [l,2-a]nH^-3-yl)-6 methoxy pyridin-4-ylamino) π bottom bite _1 _ base)_3_ Side oxypropionitrile; (R)-3-(3-(2-(6-fluoroη-moxazolo[1,2-a] ° pyridine-3-yl)-6-(2-7 bite bite -1-yl) ethoxy) spray η- 4-(Aminoamino)ββαα1·yl)_3 pendant oxypropionitrile; (R)-3-(3-(2-(6-fluoroisoxazo[1,2-a]pyridinium) -3-yl)-6-(2-(indolyl-ethyl) ethoxy) guate-4-ylamino) ketone-ΐ-yl)·3·sideoxypropionitrile; (R) -3-(3-(2-(6-fluoromethane hydrazino[1,2-a] η is more than -3-yl)·6·(2-methoxyethoxy) mouth bite-4- Amino group) (Big bite-1·yl)_3-sided oxypropionitrile; 〇R>6-(l-(2-cyanoethenyl) 唆3·ylamino)_2_(6·Fluorine Imidazo[l,2-a]pyridin-3-yl)pyrimidine-4-indene nitrile; (R)-3-(3-(2-(6-fluoro®)嗤[1,2-a]比3 侧 · · -6 -6 -6 -6 -6 · · · · · · -3 ) ) ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( 6-gas 0 m saliva [l,2-a]u than mouth>3-yl)-6-(1-methyl 102 201130835 -1H-tetra-β--5-yl) Amino) brigade-1 -yl)-3-oxo-propanoid, (R)-3-(3-(2-(6-H-oxazolo[1,2-a]acridin-3-yl) )-6-(2-methyl-2H·tetraπ sit-5-yl) gnat-4-ylamino) π-bottom-1-yl)-3-oxo-propion, (R)- 6-(l-(2-murine-ethylidene)-negative.-3-ylamino)-2-(6-murine 0 m sigma-[l,2-a]pyridin-3-yl)pyrimidine -4-decanoic acid; (R)-6-(l-(2- 乱基乙 brewing ) α 咬 -3- ylamino)-2-(6-gas 0 m α-[1,2-a]pyridin-3-yl)pyrimidine-4-decylamine; (R)-3- (3-(6-Amino-2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino-1-yl)-3-yloxy C., (R)-3-(3-(5-fluoro-2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-6-(N-heptyl) mouth咬-4-ylamino)α σ σ-1-yl)-3-oxo-propanoid, (R)-l-((R)-3-(5-fluoro-2-(6-fluoro) Imidazo[1,2-a]acridin-3-yl)-6-(N-morphinyl) Mouth sigma-4-ylamino) brigade-1 -yl)-2,3 -diyl丙-1 嗣, (R)-3-(3-(2-(6-fluoroisoxazo[1,2-ap-pyridin-3-yl)-6-decyloxy_5-(two gas A) A pharmaceutically acceptable salt or solvate or N-oxide or stereoisomer. Of great interest: 3-(4-{[(15>1-Phenylethyl)amino}pyrimidin-2-yl)imidazo[1,2-α]吼 bit-6-曱 guess,- &quot ; 3-{4-[(4-fluorobenzyl)amino]pyrimidin-2-yl}imidazo[1,2-carbidin-6-carbonitrile; 2-{4-[(2,2) -Dimethylpropyl)amino]quinazolin-2-yl}imidazo[1,2-α] 103 201130835 Pyridine-6-carbonitrile; 2-(6-fluoroimidazopyridine_3_yl) Small stupid ethyl] meridin-4-amine; monopropyl)-2-σ m 0 sit and [1,2- <3]0 than biting-3-yl-6-n ratio -3-yl 0f bit-4-amine; 3-((3Λ)-3·{[2_(6-fluoroimidazo[ΐ, 2 -β]pyridin-3-yl)pyrimidin-4-yl]amino}pyridin-1-yl)-3-oxomethoxypropionitrile; 2-(6-fluoroimidazo[丨』·冲比啶_ 3_基)_沁[(3 and) small (3,3,3-trifluoropropenyl) beridin-3-yl]pyrimidine-4-amine; (Λ)-3-(3-((2 -(6-fluoroimidazo[i,2-a] «*Bite-3-yl)pyrimidin-4-yl)(methyl)amino)piperidin-1-yl)_3_ pendant oxypropyl Nitrile; 3-((3i?)-3-{[5-fluoro-2-(6-fluoroimidazo[1,2w]pyridine-3-yl)pyrimidin-4-yl]amino} _3_ pendant oxypropionitrile; 5-fluoro-2-(6-fluoroimidazo[i,2- <3] ° pyridine-3-yl)-7\4(3 and)-1-(3,3,3-trifluoropropenyl)pyridin-3-yl]pyrimidin-4-amine; -((3i?)-3-{[2-(6-Fluoroindrazin[ι,2- chloropyridin-3-yl)-5-decylpyrimidinyl]amino} _3_ pendant oxypropionitrile; 2-(6-fluoroimidazo[Ua]pyridine-3-yl)_5-fluorenyl#[(3 and)-1-(3,3,3-trifluoropropanthene) A serotonin-4-amine; or a pharmaceutically acceptable salt or solvate thereof or an N-oxide or a stereoisomer. Preferred individual compounds of the invention comprise: 3-(4-{[(lS)-l·phenethyl]amino} sputum_2_yl) 1! rice bran [l, 2_a] 0 ratio Pyridin-6-phthalonitrile; 104 201130835 3-(4-{[(lR)-l-phenethyl]amino}pyrimidin-2-yl)imidazo[1,2-a] 0 ratio bite-6-曱 guess, 3-[4-(phenylhydrazino)pyrimidin-2-yl]imidazo[1,2-α]pyridine-6-indolecarbonitrile; 3-(4-{[(15>2-oxime)曱-1-decylethyl]amino}pyrimidin-2-yl) meroxime and [l,2-a]e ratio bite-6-carbonitrile; 3-{4-[(cyclohexyl) Amino]pyrimidin-2-yl}imidazo[1,2]anthidine-6-carbonitrile; 3-{4-[(2-oxiranyl)amino]pterin-2-yl}0 Rice bran sits and [1,2-α]π is more than bite-6-A guess; 3-{4-[(1-adamantylmethyl)amino]pyrimidin-2-yl}imidazo[1,2 -α] pyridine-6-phthalonitrile; 3-{4-[(2,2-dimercaptopropyl)amino]pyrimidin-2-yl}imidazo[1,2-anthracene] 吼-6_曱Guess, 3-{5-bromo-4-[(2,2-dimercaptopropyl)amino]pyrimidin-2-yl}imidazo[1,2-β]πΛ^-6-曱 guess, 3- {4-[(2,2-Dimethylpropyl)amino]-5-indenyl-1-yl-pilot-2-yl}0 m0 sitting and [1,2-a]11 bite- 6-phthalonitrile; 3-[4-[(2,2-dipropylpropyl)amino]-5-(2-decyloxy 0-bit-4-yl) mouth -2-yl]p m 11 sits and [1,2-&]πΛα定-6-甲猜, 3-[4-[(2,2-dimercaptopropyl)amino]-5-(2 -Sideoxy-1,2-dihydroacridine_4_yl) mouth bite-2-yl]m σ sit and [1,2-3·]σϊ^^-6-曱 guess, 3-{4 -[(2,2-Dimethylpropyl)amino]-5-10 is more than a bite-3-base mouth bite-2-base} mouth σ sit and [1,2-a] bite-6-曱Nitrile; 3-{4-[(3-fluorophenylindenyl)amino]pyrimidin-2-yl}imidazo[1,2-a]acridine 105 201130835 -6-phthalonitrile; 3-{4-[ (4-fluorobenzyl)amino]pyrimidin-2-yl}imidazo[1,2-α]pyridine-6-indolecarbonitrile; 3-{4-[(2-mercaptobenzyl)amino group Pyrimidine-2-yl}imidazo[1,2-α]吼 bit-6-曱 guess, 2-({[2-(6-cyanoimidazo[1,2_α]acridin-3-yl) Pyrimidin-4-yl]amino} decyl) piperidine-1-decanoic acid tert-butyl ester; 3-(4-{[(1-ethyl-aryl σ-chen-2-yl)methyl]amino }^σ定_2_基米唾和[1,2- <3]° ratio bite-6-carbonitrile; 3-[4_(tetrahydro-2//-piperidin-4-ylamino)pyrimidin-2-yl]imidazo[1,2-α] ° °°-6-A guess, 3-(4-(8-fluorodecane-4-ylamino)pyrimidin-2-yl)imidazo[l,2-a]acridine_6-indolecarbonitrile ; 3·[4_( 哀 己 胺 胺 ♦ ♦ ♦ 咬 基 基 ♦ ♦ ♦ 咬 咬 并 并 并 并 并 并 并 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4-Substituted hexyl)amino] 咬 -2- -2- base} 味 0 sit and [1,2-(3] 0 than bite-6-曱 guess, 3 -{4-[(5 - 经基- 2-Adamantyl)Amine]♦.Determined-2-yl} taste σ sits and [1,2-〇]0 is more than bite-6-A guess, 3-{4-[(5-base-2) -Adamantyl)Amino]Mouth bite-2-yl}Miso sitting and [1,2·ύ?]σ ratio bite-6-A guess, 2- {4_[(2,2-Dimethylpropyl) Amino}quinazoline-2_yl}imidazo[1,2_α] 0 ratio. -6-6-cha, 3-{4-[benzyl(indenyl)amino]pyrimidin-2-yl } imidazo[l,2-a] 唆-6-曱 guess, 106 201130835 3-(4·{[(15)-1-phenethyl]amine. _2_ base) Sit and [l,2·#biidine-6-carboxylic acid; 2·(6-fluoro.mazole[l,2_a]pyridine_3_yl) good [((9) phenethyl)pyrimidine-4-amine ; anti-4-{[2_(6-oxamidazo[1,2-α]pyridine-3-yl)pyrimidin-4-yl]amine Cyclohexanol; 3-(4-{[(2*SV75>5.hydroxy-2-aladamantyl]amine}}}}-yl)imidazo[1,2-α]pyridine-6 -carbonitrile; #-(2,2-dimethylpropyl)-2-imidazo[1,2·α]pyridine-3-ylpyrimidin-4-amine; #_(2,2--propylpropyl ) 2-ported rice 0 satisfies and [1,2-β]η is more than -3-yl-6-0 than bite-3_pyrimidin-4-amine; 3-(6-{[(15)-1 -phenethyl]amino} η-pyridazine_2-yl) glutamic acid [1,2-β]π-pyridyl-6-phthalonitrile; 3-{6-[(cyclohexylmethyl)amino group Pyrazin-2-yl}imidazo[1,2- <3]pyridine-6-phthalonitrile;6-(6-fluoroimidazo[ι,2-α]acridin-3-yl)-#-[(1^-1-phenethyl]«pyrazine2-amine;6-(6·amidazo[1,2-α]acridin-3-yl)-AL[(11-phenethyl]pyridazin-2-amine; 〇S)-6- (Imidazo[',2-a]pyridin-3-yl)-indole-(1-phenylethyl)pyrazin-2-amine; 6-(6-cyclopropylimidazo[1pyridin-3 -yl)-#-[(-phenylethyl)pyrazin-2-amine; 107 201130835 A4( 11 -Phenylethyl)-6-(6_ ° than pyridin-3-ylimidazo[1,2-ten Bipyridin-3-yl)π ratio π-qin-2-amine, Λ4(1-1-phenylethyl)-6-(6-pyridin-4-ylimidazo[1,2-α]pyridine-3- Base Β 嘻 胺-2-amine; phenethyl]pyrazol-4-yl)imidazo[ug 0 butyl-3-yl]° ratio ° Qin-2-amine, A4(15)-l-benzene Ethyl H-(6-phenylimidazo[1,2-α>pyridyl_3_yl) 0 is compared with °-2-enamine; 6·[6_(4-fluorophenyl)σmazole[ 1,2·α]pyridyl]-AL[(liS>i·phenethyl]pyrazin-2-amine; 3_(4·{[(3和)小(乙续醯基)°辰咬_3 _ base] amine} mouth bite_2_yl) imidazo[1,2-α]pyridine-6-indoleonitrile; 3-(4-{[(3 and)-1-(isopropyl decyl) 〇 咬 -3-yl]amino} ^ ^ ^ base imidazo[1,2-α]pyridine-6-phthalonitrile; 3-( 4-{[(3 and)-1-(cyanoethenyl) ° bottom -3-yl]amino} 鸣 _2_2_ base) imidazo[1,2- <3] «Bipyridine-6-indoleonitrile; 3-(4_{[(3/?)-1-propenylpiperidin-3-yl]amine}}} [1,2-α]pyridine-6-phthalonitrile; Η4·({(3 and)·Η(1_cyanocyclopropyl))] 〇 啶 _ 3 3 3 3 3 _ _ _ _ 2-based] π-mial-[1,2-β]pyrene than biting _6·carbonitrile; 3-(4-{[(3 and)-1-(methoxyethenyl)piperidine _3 _ base] amino} pyrimidine_2_yl) ° rice saliva [1,2- <φ ratio bite-6-carbonitrile; 3-(4_{[(3 and) small (3-carbyl-3-methylbutanyl)-derived _3_yl]amine mimic-2-yl) Wow [ΐ,2-β]υ is more than 唆-6-carbonitrile; 108 201130835 3-(4-{[(3幻-1-(3,3-dimercaptobutyl)piperidin-3-yl] Amino}pyrimidin-2-yl)imidazo[1,2-α]pyridine-6-phthalonitrile; 3-(4-{[(3/?)-1-(1/ί-imidazo-1-4 -ethylidene)piperidin-3-yl]amine} mouth bite_2_mimiindole[1,2- <2]0 than bite-6-method, 3-[4-({(37?) small [(5·cyano π-pyridin-2-yl)carbonyl]piperidin-3-yl}amino) Pyrimidine-2-yl]imidazo[1,2-β]acridin-6-indolecarbonitrile; 3-(4-{[(37?)_1_(3,353-di 1 propyl) Amino group} 喊 咬 -2- 基 基 -2- -2- -2- -2- 并 并 并 [ [ [ [ [ [ [ [ [ [ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 [ [ [ [ Imidazo[1,2w]acridin-3-yl)pyrimidin-4-yl]amino}-Agv-dimercaptopiperidin-1-ylamine; 3·{4·[((3幻- 1_{[(2&4) 2-cyano-4-fluoropyridin-1-yl]carbonyl} ketone-3-yl)amino group] pain bite-2-yl} taste σ sit and [1, 2-β]σΛ^-6-A guess, 3-(4·{[(37?)-1-(5-cyanoacridin-2-yl)piperidin-3-yl]amino}pyrimidine- 2-Based rice σ sit and [1,2e] ntb _ _6-甲猜, 3·(4·{[(37?)-1_(4-cyano-2-fluorophenyl)piperidine- 3-yl]amino}pyrimidin-2-yl) 米米σ sits [1,2_α]πΛ^_6-曱 guess; 3_{4_[[(37?)_1_(cyanoethenyl)piperidine- 3-yl](indenyl)amino]pyrimidin-2-yl}-salt and [1,2_"] 〇 咬-6-6-A guess, 3·(4-{[(35)_1-(cyanide)基 )) piperidin-3-yl]amino}pyrimidin-2-yl) 米米σ sit and [1,2-ί?] ϋ 咬 -6-6-曱 guess, cis-3-(4- {1-(random basis )-4-曱基.辰咬-3-基]amine} mouth bite•2-base) °米σ sit and [1,2-α]ϋ bite·6-曱 guess, cis-3-( 4-{1-(Ethyl sulphate)-4-methyl. ° 定 -3-yl]amino} 喊 咬 -2 · yl) imidazo[1,2-α] ton pyridine-6- Benzonitrile; 109 201130835 3-{4-[[1-(ethylsulfanyl)-4-methylpiperidinyl-3-yl](methyl)amino]pyrimidin-2-yl}mi. [1,2_^^ is 0 to _6_carbonitrile; 3-((3i?)-3-{[2-(6-fluoroimidazo[1,2-α]pyridine-3-yl)pyrimidine_ 4_yl]amino}pyridin-1-yl)_3. pendant oxypropionitrile; (i〇-l-(3-(2-(6-fluoroimidazo[i,2_a]n pyridine) _ yl)pyrimidin-4-ylamino)piperidine-1-carbonyl)cyclopropane carbonitrile; 2-(6-fluoroimidazo[1,2·α]pyridine _3_yl) good [(3 illusion (3,3,3_trifluoropropyl) π bottom bit-3-yl] whistle-4-amine; 2_(6·fluoroimidazo[1,2·α]pyridine _3·yl) good [ (3i?)-l-(l//-pyrazol-4-yl-yl)11-bottom-3-yl] shouting 4-amine; (cyanomethyl)-3_{[2·(6· Fluorobutrazol [1,2_α]° pyridine _3_ base) 喷 _4·yl]amino}-7V-methyl ketone-1-amine; 2-((3 and)- 3-{[2-(6-fluoroimidazo[1,2-bromopyridyl_3_yl)cyclopyridine_4_yl] lie base}-bit-1-yl)-2-methylpropyl Amine; 2-(6-fluoroamidoxime [ΐ,2-α] ° than -3-yl) 曱基善[(3/?)-1-(3,3,3-trifluoropropanthene Base) n辰 bite _3_ base] mouth bite _4-amine; (/?)-3-(3-((2-(6- It 咪 sit and [l,2-a]β than bite- 3-yl) ringing-4-yl)(fluorenyl)amino) bistidin-1-yl)_3. pendant oxypropionitrile; (8)-1-(3-((2-(6-fluoro) And [l,2-a] ° than -3-yl) mouth bit -4-yl) (fluorenyl)amino) piperidine-1-carbonyl) cyclopropanecarbonitrile; 3- ((3 and)- 3-·{Ethyl[2-(6- defeated 0 m saliva[1;2- <3]° ratio -3-yl) -4-yl]amino}piperidin-1-yl)-3-oxo-propanonitrile; /V·ethyl-2-(6-fluoro η米σ sits and (1)-^Bu than bite-]· Base HV-[(3i〇-l-(3,3,3-trifluoropropenyl) tour-3-yl] shouts tr-4 -amine; 110 201130835 3-((3 Magic-3-{(cyclopropylmethyl)[2-(6-fluoroimidazo[1,2-α]acridin-3-yl)) Amino}yl)-3-lateral gas-based cyan, (cyclopropyl)-2-(6-fluoroimipirin[1,2- <3] 0 to -3-yl)-Aq(3^-l-(3,3,3-trifluoropropenyl)piperidin-3-yl]pyrimidin-4-amine; 3-(( 3Λ)-3-{[5-fluoro-2-(6-fluoroimidazo[1,2-β]pyridin-3-yl)pyrimidin-4-yl]amino}Nymidine-1-yl)-3 - oxypropanoid, 5-gas-2-(6-gas, ^&[1,2-α]πΗ:^-3-yl)-A4(3i?)-l-(3,3, 3-trifluoropropionyl)piperidin-3-yl]pyrimidine-4-amine; 3-((3i?)-3-{[2-(6-fluoroimidazo[1,2-α]acridine -3-yl)-5-decylpyrimidine-4-yl]amino} dentate-1-yl)-3-oxo-propanone gamma, 2-(6-fluoroimidazo[1,2- ]]pyridin-3-yl)-5-methyl-indole 4(3 and)-1-(3,3,3-trifluoropropenyl)piperidin-3-yl]pyrimidine-4-amine; 3- ((37?)-3·{[2-(6-fluoroimidazo[1,2-α]acridin-3-yl)pyrimidin-4-yl]amino}}D ratio 唆-1-yl) -3-Sideoxypropyl, 3-{4-[4-(cyanoethyl)-1,4-diazepan-1-yl]pyrimidin-2-yl}imidazo[1 , 2-α]π-pyridyl-6-phthalonitrile; 3-((3 magic-3-{[5-gas-2-(6-fluoroimidazo[1,2-α]acridin-3-yl) Pyrimidine-4-yl]amino}Bindyl-1-yl)-3-oxo-propanoid, 3-((3 magic-3-{[2-(6·fluoroimidazo[1,2- α]Acridine-3-yl)pyrimidin-4-yl]amino}N-唆-1-yl)_2,2-dimethylpropy, 2-(37 ?)-3-{ρ-(6-fluoroimidazo[1,2-4 acridine-3-yl)pyrimidin-4-yl]amino}piperidin-1-yl)acetamide, or a pharmaceutical thereof A pharmaceutically acceptable salt or solvate or hydrazine-oxide or stereoisomer. 111 201130835 The present invention further provides a novel imidazopyridine derivative of formula (i), or a pharmaceutically acceptable salt or solvent thereof a compound or an N-oxide or a stereoisomer or a deuterated derivative:

(Formula I) wherein m, X, Y, Z and & to R9 are as defined above, the compound is not: 6-millimeter σ sits and [1,2-a]π is more than -3-yl- N-(3R)-3-branches-2-yl-pyramine hydrochloride; 6-m-m-α sits and [1,2-a] ° is more than -3-yl-N-(3S)- 3-Bent bityl-2-σ-proline, 6-(6-chloroimidazo[1,2-a]pyridin-3-yl)-N-(3R)-3-piperidinyl-2-pyridinium 6-(6-methoxyimidazo[l,2-a]pyridin-3-yl)-iNi-(3R)-3-piperidinyl-2-π ratio π-h-amine, 6-port Rice σ sits and [1,2-a] bites -3 -yl-N-(3R)-3 -π ratio 11 each bite base-2-α ratio 0-Qinamine; 112 201130835 N-(4,4- Dioxane-3-birth β sits and [l,2-a]e is more than -3-yl-2-pyrazineamine hydrochloride; 6-imidazo[1,2-a]pyridin-3-yl -N-[(3R,4R)-4-methyl-3-pyrrolidinyl]-2-pyrazinamine; N-(3R)-3-npyrrolidyl-6-[6-(trifluoro Mercapto) imidazo[l,2-a]acridin-3-yl]-2-indoleamine, α,α-dimethyl_3-[6-[[(3R,4R)-4- Mercapto-3-pyrrolidinyl]amino]-2-indole-methyl]-salt-[1,2-&]° ratio bite-6-methanol; 6-imidazo[l,2-a] Pyridin-3-yl-3-indolyl-N-(3R)-3-piperidinyl-2-pyrazinamine; (2R,3R)-N-[6-(7-oximeoxy And [1,2-a]pyridin-3-yl)-2-pyrazinyl]-2-mercapto-1-azabicyclo[2.2.2]oct-3-amine; 3-imidazo[1, 2-a]«pyridin-3-yl-5-[(3R)-3-piperidinylamino]-2-pyrazinium nitrile phthalate; 3-[6-[(3R)-3- Piperidinylamino]-2-pyrazinyl]-imidazo[1,2-a] 吼-7-曱, N-[(3R,5S)-5-(difluoroindolyl)-3 -«Byrridinyl]-6-imidazo[l,2-a] 0 is more than indole-3-ylamine, N-[(3S,4R)-4-fluoro-3-piperidinyl]-6 -imidazo[1,2-a]pyridin-3-yl-2-pyrazinamine; N-[(3S,4S)-4:fluoro-3-piperidinyl]-6-imidazo[1,2 -a] acridine-3-yl-2-pyrazinamine; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3S,4S)-4-decyloxy-3- Piperidinyl]-2-atb°qinamine, 113 201130835 6-Imidazo[1,2-a]pyridin-3-yl-N-[(3R,6S)-6-mercapto-3-piperidinyl ]-2-pyrazineamine citrate; 6-imidazo[1,2-a]acridin-3-yl-N-[(3R,6R)-6-methyl-3-piperidinyl]- 2-pyrazinamine formate; 6-[7-[2-(1-methylethoxy)ethoxy]imidazo[[,? 々].比 _ 3 _ _ _ _ _ _ 定 定 定 定 定 定 定 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; - oxazolo[1,2-a] bite-3-yl-2-° ratio °qinamine; N-[(3S,4S)_4_ethoxy-pyridyl_3_yl]_6_ (mouth Mizozo[ua]pyridin-3-yl to oxime-2-amine; 6-imiphtho[l,2_a;hb pyridine-3-yl-3-methoxy-N-(3R)_3-piper Pyridyl-2-pyrazinamine 2,2,2·trifluoroacetate; decyl imidazo[l,2-a]pyridine each)_n_(3R)-3-pyridinyl-2-pyrazine Amine; 6-(7-nonylimidazo[1,2-a]pyridine-3-yl)-N-(3R)_3-piperidinyl-2-pyrazinamine; N-(3R)-3-piperidine -6-[6-(trifluoromethyl)imidazo[丨,2_a]pyridine-3-yl]_2-βpyrazine; N-(3R)-3-piperidinyl-6-[7- (Trifluoromethyl) imidazo[丨,2_a] „bipyridin-3-yl]decylamine; ,6-(7-ethylimidazo[丨,2_a] „biidine_3_yl) Piperidinyl-2-pyrazinamine; 6-[6-(1-methylethyl)imiindole[l,2_a]0 is more than _3_yl]-N_(3R)_3· fl σ定基-2-π-pyrazinamine; 114 201130835 6-(7-azamidazo[1,2-a]acridin-3-yl)-N-(3R)-3-piperidinyl-2-indole Nazinamide; N-[(3R,4R)-4-fluoro-decyl]-6_°米〇 sits and [l,2- a]e ratio β--3-yl-2-pyridazinamine; 6-[5-[(3-indolyl-3-oxetanyl) decyloxy]-1 Η-benzo-flavor β -1-yl]-N-(3R)-3_piperidinyl-2-pyrazinamine; 6-midazo[1,2-a]n ratio bit-3-yl-N-(3 S) -3 - indole-2-ylpyrazine; 6-(6-methylimidazo[l,2-a]acridin-3-yl)-N-(3R)-3-indolyl 2-ylpyrazinamine; 6-(7-methylimidazo[l,2_a]pyridine-3-yl)-N-(3R)-3-indolyl-2-pyrazineamine; 6- (7-methoxyimidazo[l,2-ap-pyridin-3-yl)-N-(3R)-3-indolyl-2-ylamine; N-(3R)-3-吼Rr-pyridyl-6-[7-(trifluoromethyl carbazole [1,2-&] or pyridin-3-yl]·2-σ-pyridamine; 6·imidazo[1,2 -a]pyridin-3-yl-indole-(3-indolyl-3-piperidyl)-2-pyrazinamine; 6-(6-methoxyimidazo[1,2-a]pyridine-3 -yl)-N-(3R)-3-pyrrolidinyl-2-pyrazinamine; 6-(7-ethylimidazo[1,2-a]"bipyridyl)-N-(3R -3- oxaridinyl pyrazinamide; methyl ethyl) oxazolo[Ha]acridine _3• group; |_N_(3r)_3_ ° ratio slightly biting base _2• oxazinamide; 115 201130835 6-(5-Methylimidazo[l,2-a]pyridine-3-yl)-N-(3R)-3-pyrrolidinyl-2-pyrazinamine; 6-(7- Imidazo[i,2-a]npyridyl_3_yl)-N-[(3S,4S)-4-fluoro_3_indolyl]-2-pyrazinamine; N-[(3R,5S -5-(|L-methyl)-3-indenylpyridyl] each of the oxazolo[l,2-a] valences of 0--3-yl-2-π-pyridylamine; N-[(3R , 5S) _5-(fluoromethyl)_3_ oxazolidinyl]_6_[7-(trifluoromethyl)imidazo[l,2-a]pyridin-3-yl]-2-pyrazinamine; {6-[(3R)-piperidin-3-ylamino]β-pyridin-2-yl)-salt and [丨, 2a] acridine-7-nonylamine; 6-(6-fluoroimirene And [i,2_a] than bite base)_N (3R)_3pyridinyl_2_pyrazinamine; 6-(6-fluoroimidazo[[beta]3)_Ν_[(3Κ,6Κ)_6曱_3_ 派基基]-2-. Butyramine; N_[(3R,5S)·5-fluoroindolyl)_3·°pyrrolidyl]-6-[7·(trifluoromethyl)imidazo[l,2-a]pyridine_ 3_yl]2_pyrazinamine; 6-(6-fluoroimidazolium, 2_a]pyridine-3-yl)_n[(3s,4r)_4_fluoxapyranyl]-2-nitazinamine; 6-(6-fluoroimidazo[丨,2_a]pyridine·3-yl)_N_(3R)_3 pyrrolidinyl-2·pyrazinamine; H6-fluoro miso sitting and buffering ratio ^-based called (10) state Winter gas ^ ratio 11 each bite base]-2-n azine amine; 6 (6 fluoroimidazo[[ 吼 j 基 基 base) _n_[(3r,6S)_6·methyl_3· BTS base]- 2-»Bismamine; 116 201130835 6-(6-Fluoro, sit and n, 2_a]D than 唆_3_yl)n[(2r, called 2methyl_3·11 bottom 0 base)-2 - oxazinamide; 6_(6· fluoroimi-β sitting and (10) ♦ than biting _34> n_[(2s, 3r) 2 methyl-> 0 〇 〇 ] ] -2- 嗓 -2- -2- -2- ; ; ; Methyl hydrazino and [l,2-a] money-3-yl 4 (3_methyl scale bite _3 base) β is a 2-amine, 6-imidazo[1,2♦ than pyridine-3. Ν···[(28,3Κ)_2_methyl_3·piperidinyl]-2_pyrazinamine; 6-(7-azamidazo[l,2_a]pyridinyl)_N_[(2R, 3R)·2曱基-3_ BTS]-2-α-proline; 6·(7·Chloramidazo[l,2-a]pyridine)-N_[(2S,3R)_2曱·3_ Loudi Olefin]-2-11-pyazinamine; 6-imidazo[1,2-a]acridin-3-yl-N-[(2R,3R)-2-methyl-3-piperidinyl]- 2-pyrazinamine; N-(3R)-3-Butryridyl-6-[7-(2,2,2-trifluoro-l-methylethoxy)isoxazo[1,2-ap比 _ 3 _ _ _ 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 N-(3R)_3_旅唆基_2_D比azinamide; (18,4 ft, 611) ritual (6-imidazo[1,2-micropyridyl_3_yl_2_„pyrazinyl)_2_ Azabicyclophene P.2.1]hept-6-amine; (lS,4R,6R)-N_[6-(7-decyloxyimidazole [i,2-a]pyridin-3-yl)-2- ° Biazinyl]_2. azabicyclo[2.2.1]g-6 amine; (lS,4R,6R)-N-[6-(6-l imidazo[i,2-a]acridine-3_ ))-2-oxazinyl]-2-azabicyclo[2.2.1]hept-6-amine; 117 201130835 6-(7-azamidazo[1,2-a]pyridin-3-yl)- N-[(3R,4R)-4-methyl-3-0-benzaridinyl]-2-pyrazinamine; N-[(3R,4RH_(fluoromethyl)-3·°pyrrolidyl] -6-imidazo[1,2-a] 0 is more than -3-yl-2-pyrazine; 6-mithio[1,2-a]pyridin-3-yl-N-[(2S , 3R)-2-methyl-3-piperidinyl]-2-pyrazinamine; 6-imidazo[1,2-a]pyridin-3-yl-N-[(2R,3S)-2· Methyl-3·peri N-(3R)-3-indenylpyridinyl-6-[7-(2,2,2·trifluorosuccinylmethylethoxy)isoxazole[l,2 -a]pyridin-3-yl]-2-pyrazinamine; 3-[6-[(3R)_3-D-dinylamino]_2·pyrazinyl]isoxazo[12_&]pyridine-7 - alcohol; 6-imidazo[l,2-a]pyridine-3-yl-N-[(2R,3R)-2-methyl-3-piperidinyl]-2-pyridinium; 6-imidazole And [1,2-a]pyridin-3-yl-N-[(2S,3S)-2-indolyl-3-piperidinyl]-2-pyramine; 6-(6-fluoroimidazo[ ΐ, 2-φ 啶 ··3_yl)-Ν·[(3Μ8)_4_methyl·3_pyrrolidinyl]-2-pyrazinamine; 6·imidazo[1,2-a]pyridin-3-yl -N-[(3R,5R)-5-mercapto-3-pyrrolidinyl]-2-pyrazinamine; 6-[7,3-dimethylbutoxy)imidazopyridin-3-one ]_N-(3R)_3·Gantylene·2_ηBiazinamide; 3-[6-[(3R)-3-Brigade. Fixed amino group] ~ ratio. "Qinji] ten sitting and acridine-6-methanol; 201130835 6-(7-methoxy sigma-salt[l,2-a]e than indole-3-yl)-N-[(3R,4R) 4-phenyl-3-pyrrolidinyl]-2-pyrazinamine; 6-(2-mercaptoimidazo[i,2-a]pyridin-3-yl)-N-(3R)-3- Piperidinyl-2-pyrazinamine; 6-[7-[(3-indolyl-3-oxetanyl)methoxy p-moxazolo[ny 0-bit-3-yl]-N -(3R)-3-b is more than guanamine-2-° than decylamine; H7_[(3_methyl_3.oxetanyl)methoxy]imidazo[Ua] bite·3 ·-]-N-(3R)_3 brittle base 2-n-pyrazine; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,5R)-5- Oxy-3-piperidinyl]-2-decylamine; 6-imidazo[1,2-appyridin-3-yl-N-[(3R,5S)-5-(methoxy fluorenyl) -3- oxaridinyl] 2-pyazinamine; 6-isoxazo[l,2-a]«pyridin-3-yl-N-[(3R,5S)-5-[(l -Methyl ethoxy)methyl]-3-indolyl]-2-n-pyrazinyl; N-(6-flavored tr-[1,2-a] ° than -3-yl- 2-u-bi-yl)-2-azabicyclo[2.2.1]hept-6-amine; H6-[(1S,4R,6R)·2-azabicyclo[2,2.1]hept-6-amine Base]·2-n-r-azinyl]-imidazo[l,2-a; K-pyridine-7-carbonitrile; 6-(1_fluoro-azolo[l,2_a]pyridyl)_N_[(2R 3S)_2·曱基·3_派唆基]-2-°Bazinamide; 6_(1·fluoroimidazo[l,2-a]pyridine!yl)_N_K2R,3R)·2·曱基_3· 0 pyridine group]-2-pyrazine amine; 119 1 _(1_fluoroimidazo[l,2_a]pyridyl)_n-[(2S,3R)-2-mercapto-3-0 bottom base] -2-oxazinamide; 201130835 3-[6-_-3·Leskinamine]_2 “Biazine^

Pyridyl-7-phthalonitrile; J 3-[H[(3R,4R)-4·methyl each aryl]amino]Id is more than imidazo[l,2-a]pyridine-7-indeneonitrile; 3 [6 [[(3R,5S)-5-(methoxymethyl)_3_β is slightly succinate] amino] 比 基 ] ] ] l l [l, 2-a] > nt ^ -7 -carbonitrile; 3-[6-[[(3R,5R)-5-methyl_3-t each <yl]amino]_2"pyrazinyl]-imidazo[l,2-a]pyridine -7-carbonitrile; 6-imidazo[1,2-a]pyridin-3-yl_N-[(3S,4R)_4-oxooxyspyrrolidinyl]2-pyrazinamine-; 3- [6-[[(3R,4R)-4-indolyl-3-pyrrolidinyl]amino] gastric 2_pyrazinyl]-imidazo[l,2-a]pyridine-7-carboxamide; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,5S)-5-(propoxyindolyl)-3-pyrrolidinyl]-2-pyridinium; N -[(3R,5S)·5-(ethoxyindolyl)·3_β piroxime]_6_mi. Sit and [l,2-a]pyridine-3-yl-2-pyrazinamine; 6-imidazo[l,2-a].pyridin-3-yl-N-[(3R,4R)-4-(l-methylethyl)-3-pyrrolidinyl]-2-pyrazine Amine; 6-imidazo[l,2-a].pyridin-3-yl-:^-[(38,411)-4-(2,2,2-trifluoroethoxy)-3-°Bilo咬 base]-2-° than decylamine; N-[(3R,4R)-4-ethyl-3-pyrrolidinyl]-6-imidazo[1,2-a]pyridin-3- -2-n-pyrazinamine; N-[(3R,4R)-4-cyclopropyl-3-pyrrolidinyl]-6-imidazo[1,2-a]pyridin-3-yl-2- ^βQinamine; 120 201130835 (3R,5R)-5-[(6-_Saliva[1,2-&]° than bite-3_yl-2-'»pyrazinyl)amino]- 3-Brigade october; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,4R)-4-indolyl-3-piperidinyl]-2-° guanamine ; 6-(7-chloroimidazo[i,2-a]0 pyridine-3-yl)-N-[(3R,4R)-4·methyl-3-pyranyl]-2-n ratio Azinamide; 6-(8-methylimidazo[1,2-a]pyridine-3-yl)-N-(3R)-3-piperidinyl-2-ntbeqinamine, 6-[7-( 1-methyl-1H-pyrazol-4-yl)imidazo[i,2-a]pyridine_3·yl]-N-[(3R,4R)_4-methyl·3·η ratio slightly biting ]_2" than the amine; N-[(3R,4R)-4-cyclopentyl-3-n-pyridyl]_6_(7_decyloxyimidazo[l,2-a]e than bite- 3-yl)-2-n-pyridazinamine; N-[(3R,4R)-4-cyclopropyl-3-»pyrrole]_6-(7·decyl imidazo[1,2- &]° than -3-yl)-2-*»bistamine; 6-imidazo[l,2-a]pyridin-3-yl-3-decyloxy·ν_(3ΙΙ)·3- Pyrrrolidinyl-2-pyridazinamine; 6-[7-[2-(1-decylethoxy)ethoxy]imidazo[p,2a] η-pyridyl·3·yl]-N-(3R )-3-n ratio Bite base - 2 ° ratio of qinamine; 6-mipropion [1,2♦ than bitten-3-yl-3-methyl_N_ (3R> 3_pyrrolidinyl-2-σ-specific amine, » 6_(6_ clomiphene [12-a]0 is more than -3-yl)-N-[(2S.",3R)-2-mercapto-3·0 bottom bite]_2·α ratio 11 Qinamine; 6-(6-chloroimipiro[l,2-a]n than bite 3-yl)_n_[(2R,3R)-2-methyl·3_piperidinyl]-2-pyrazine Amine; 121 201130835 N-[(2S,3R)-2-methyl-3_ slightly bitiyl]-6-[6-(trifluoromethyl)p-sodium[l,2-a]pyridine-3 -yl]-2-pyrazinamine; N-[(2R,3R)_2_methyl_3_π bottom base]_6_[6_(trifluoromethyl)p-mazole and 6-(6-azamidazo[1)2 々]pyridine each)-N_[(3R,4R)_4_methyl_3_ each bite]-2-n ratio n-Qinamine; 6-(6-azamidazo[丨,2_a]pyridine_3_ Base) _ Ν _ (44 · difluoro _ 3 sent bite) -2- ° than decylamine; N- (4,4-difluoro·3 · piperidinyl) _6-[6-(trifluoromethyl) taste Oxazolo[uy 0 is more than -3-yl]-2-n than decylamine; α,α-dimethyl_3_[6_[(3r)_3_piperidinylamino]_2·pyrazinyl] Zoxa[l,2-a]pyridine-6-nonanol; 3-[6-[(3R)-3-piperidinylamino] 2 pyrazinyl]-isoxazo[丨, 2^ pyridine -6_amine; 6_(7_flumidazo[1,2-a]pyridine_3·yl)_N_(3R)·3·piper ··2_ pyrazinamide; j fluoromiso-[1,2-φ-pyridin-3-yl)-N-[(3R,5S)-5-(decyloxymethyl)·3-πpiro Bite base]-2-° than decylamine; bazinyl)amine (2S,4R)-4-[(6_ imipo[i,2-a] 吼_3-yl-2-yl]-2· Pyrrolidine methanol; N-[(3R,5S)-S.(methoxymethyl)-34^1^yl]_6_(7A σ sits and [l,2-a]n is more than -3-yl -2·β-barbaramine; N-[(3R,5S)-5-[(l-decylethoxy)methyl]_3_indolepyridinyl]·methyl n-miso-[l , 2_a]fl is more than 唆3·yl)·2·σ is amide; 122 201130835 N-[(3R,5S)-5·(ethoxymethyl)·3_πpyrazole [1,2- a]pyridin-3-yl)-2-pyrazinamine; soil]- _methylimidate 6-(7-methoxyimidazo[7] than f Ν-[(_)·5-[(1·methyl) Ethoxy)methyl]·3·scale butterfly ~ than °Nyrene, ,N [(3R,5S)-5_(ethoxymethyl peak 吼心定基]·6 (7·methoxy 17 m And [1,2 - a] ^ is more than -3 -yl) - 2 - decylamine; 6 - (7-chloro-flavor α sitting and [u_a]a than biting _3_ base) _n_[(3r, It is called 5(methoxymethyl)-3-npyrrolidyl]-2-pyridazinamine; (2S,4R)-4-[[6-(7-azamidazolium π, 2♦ than bite 3 Base bisazinyl]amino]-2-° ratio slightly biting methanol; 6-(6- Chlorinated sulphur [1,2-a] ° ratio -3-yl)-N-[(3R,5 S)-5-(nonyloxyindenyl)_3· oxaridinyl]_2_pyrazine Amine; 6·imidazo[l,2-a]pyridin-3-yl-5-methyl_N_(3R>3-benzaridinyl-2-pyrazinamine; N-[(3R)-4, 4_Difluoro-3-Big bite base]_6_ 咪β sit and [i,2_a]n bite j•yl-2-0 to 11-Qinamine; 1^-[(38)-4,4-difluoro- 3-11 bottom bite base]-6-imi-[l,2-a]π ratio -3-yl-2-pyrazinamine; 6-imidazo[1,2-a]pyridin-3-yl -N-[(3S,5S)-5-decyloxy-3-piperidyl]-2-oxazinamine; 6-imidazo[1,2-a]pyridine-3-yl-N-[( 3S,4S)-4-decyloxy-3-piperidinyl]-2-pyridazinamine; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,4R)-4 _methoxy-3-piperidin 123 201130835 pyridine]-2-pyrazinamine hydrochloride; 3_[6-[[(2R,3R)-2-indolyl-3-piperidinyl]amino]- 2-pyrazinyl] "mizozo[l,2-a]pyridine-7-carbonitrile; 3-[6-[[(3R,4R)_4-cyclopropyl-3-pyrrolidinyl]amine ]-2-pyridyl]--salt and [l,2-a]a ratio bite-6-carbonitrile; HH[(3R,4R)·4-cyclopropyl each, each bite group] amine group ]_2_Pyrazinyl]-imidazo[l,2-a]pyridine-7-carbonitrile; (2S,3S)-N-[6-(7-methoxyimidazo[i,2_a]吼_3·yl»bazinyl]-2-methylazirazocyclop.2.2]oct-3-amine; 6-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-N -[(3R,5S)-5-(methoxymethyl)-3-n piroxime]-2-pyridazinamine; 3. oxazolo[l>a]pyridyl ice-based _5_[( 3R)··································· -2-βΛβ-Qinamine; 2-[[3-[6_[(3R)-3-indolylamino]]2· π-pyridinyl]imidazo[1,2-&]°°° -7-7-yl]oxy]-ethanol; (2S)-2-[[H6-[(3r)-3_^ lysylamino]_2douqin] miso[l,2-a]pyridine _7_yl]oxy]propanol; (2S)-2-[[3-[6-[(3R)_3-indolyl]_2•pyridazinyl] miso[l,2 -a]n-pyridin-7-yl]oxy]-1-alcohol; ♦- dentylamino]_2 "noise-based" taste and [l,2_a] ° bite _7_yl]oxy] -2-internal alcohol; (2R)-2-[[3-[6-[(3R)-3i „ each dimethylamino]_2_mercapto] oxazole 124 201130835 and [lj-ap than bite- 7-yloxy]propanol

2·[[3-[6·_·3« ylamino]_2_%azinepyridin-7-yl]oxy]-ethanol; L ' aJ 6+ sitting and [U♦ ratio bite_3_base_5 _Methyl_N_(3R>3♦ each bite base-2-° than decylamine, (called 31 (6-gas imipenone [u♦ ling 3 base) _2" 嘻 ]] aminyl]-I- 0 咬 1,1-didecylethyl formate; (3R)-3-[[6-(6-oxime-imidazolyl p,2_a] n-pyridyl_3_yl)_2_σpyrazinyl]amine Base]-1-σ辰 bition formic acid 1,1_dimethyl-ethyl hydrazine; (3R)-3|[7-(amino-based)·sitting and resembling a small bite ^-based^pyridyl]amine Base H-0 bottom bitillic acid 1,1-dimethylethyl; (3R,4R)·4-ethoxy_3 repair light and [1,2♦ ratio base 2_ππ-pyridyl) amine group [-1-R piperidinecarboxylic acid phenylmethyl ester; (3R)-3-[(6-flavorip[i,2-a]acridine_3_yl-2-oxazinyl)amine] 1,1-dimethylethyl piperidinecarboxylic acid; (3S) 3 [(6-flavor β sitting and [ι, 2_φ ratio bite_3_yl-2"pyrazinyl)amino] piperidinic acid 1 ,1-dimethylethyl ester; (3R)-3-[(6-mimi-[[,2-φ-pyridyl]-3-yl-2-yl]pyridyl)amino]pyrrolidinic acid 1,1-dimethylethyl ester; (3R,4R)-3-[(6-imidazolyl-to-bito-3-aminopyridinyl)amino]-4-methyl-1-pyrrolidinecarboxylic acid Dimethyl b ; (3R)-3-[[6-[6_(trifluoromethyl)) 0 sitting and like ♦ than biting _3 base] 2 〇 嗪 嗪 ] ] ] 胺 胺 胺 胺 1 1 1 1 1 1 Dimethylethyl ester; (3R,4R)-3-[[6-[6-(l-trans-yl-i-methylethyl) methoxy-salt [by small ratio 125 201130835 疋3 base] 2 ratio Azyl]amino]_4_fluorenyl sulphonic acid I, dimethyl dimethyl ether; (3R)-3-[(6-imidazo[na]pyridine_3_yl 3 methyl _ 2-oxazinyl)diaminoethylamino]-1-piperidinecarboxylate; (3R)-3-[(5.cyano-6-imidazo[[pilotylpyridinyl-2-pyrazinyl)) 1,1-dimethylethyl ester of amino]-1-piperidinecarboxylic acid; H6-[[(3R) small [(8)-indoleyl ethoxy]] 2-°Byrazinyl]-imidazo[l,2_a]pyridine_7-carboxylic acid decyl ester; (2S,4R)-2-(disindolyl Η[[6-6 oxazolo[i,2-a Acridine-3-yl-2-pyrazinyl)amino]-1-pyrrolidinoic acid 1, 丨-didecylethyl ester; (3R,4S)_4·fluoro·Η(6·isoxazole [l,2-a]pyridin-3-yl-2-pyrazinyl)amino]-1-benzylidene phenylmethyl ester; (3R,4R)_4·fluorine_3-[(6-flavor Oxazolo[l,2_a]pyridinyl-2-pyrazazinyl)amino]-1-piperidinic acid phenylmethyl ester; (3R,4R)-3-[(6-p米嗤和[l ,2-a] ° than bite-3 -yl-2-** ratio c-methyl)amino] 4-methoxy-1-piperidinecarboxylic acid phenylmethyl ester; (2S,5R)-5-[(6·米嗤和[l, 2-a] ° than benzyl-3-yl-2-π oxazinyl)amino]-2-methyl-1-piperidinecarboxylic acid phenylmethyl ester; (2R,5R)-5-[(6-imidazole And [l,2-a]"pyridin-3-yl-2-pyrazinyl)amino]_2-methyl-1-piperidinecarboxylic acid phenylmethyl ester; (3R)-3-[[6 -[7-[2-(l-methylethoxy)ethoxy]imieno[i,2_a]pyridin-3-yl]-2-pyrazinyl]amino]] ,1_dimethylethyl ester; (3R)-3-[(6-imidazo[l,2-a]acridin-3-yl-3-methoxy-2-pyridinyl)amino] 1,1-dimethylethyl -1-piperidinecarboxylate. 126 201130835 The above compounds are disclosed in WO2010/016005. In general, the compounds of formula (I) do not comprise the compounds disclosed in WO 2010/016005, including the salts, solvates and stereoisomers disclosed therein. Usually, the compound of formula (I) is not mwa and [l,2-a]0 is more than indole-3-yl-N-(3-decyloxy)-2-indazinylamine; N-(4 - gas phenyl)_6-(2-mercaptoimidazo[i,2_a]pyridin-3-yl)-2-pyrazinamine; N-(4-filled phenylmethylimidazolidinium; N-( 4-methoxyphenyl)_6_(2-mercaptoimidazo[y-appyridyl-3-yl)-2-pyrazinamine; N-(4-ethoxyphenyl) each (2-indenyl) Imidazo[i,2-a]acridin-3-yl)-2-pyrazinamine; 1-[4-[[6-nonylimidazo[l,2-a]° pyridine-3- ))-2-pyrazinyl]amino]phenyl]-ethanone; N1,N1-dimercapto-N4-[6-(2-methylimidazo[l,2-a]pyridine-3- Base)-2-n-pyrazinyl]_ι,4-phenylenediamine; Ν-(4·phenylene)-6-(2-methyl sigma-salt[l,2-a]° than bite- 3-yl)·2-0-pyrazinamine; Ν-(3_ desert', phenyl)-6-(2-methylimidazo[l,2-a]acridin-3-yl)-2^ Biazinamide hydrobromide. The above compounds are disclosed in WO2010/002985. In general, the compounds of formula (I) do not comprise the compounds disclosed in WO 2010/002985, including the salts, solvates and stereoisomers thereof as disclosed in 127 201130835. Typically, in the compound of formula (I), wherein m, X, Y, Z and heart to R9 are as defined above, the limitation is that when Y represents a nitrogen atom and X represents a -CR_9 group, then When 8 represents a 5- to 6-membered heterocyclic group containing a nitrogen atom, the nitrogen atom is not bonded to a -Z-(CR6R7)m- moiety which is not a third butoxycarbonyl group or a benzoquinone The substituent of the oxycarbonyl group is substituted; and when R8 represents a phenyl group, m is an integer of from 1 to 3. According to one embodiment of the invention, the compound of formula (I) can be prepared by the following synthetic route as illustrated in Figure 1.

Compounds of formula (I) wherein X or Y are nitrogen atoms and the remaining atoms are 128 201130835 CRii groups are described in the literature (J. 〇g. c/zem. 2007, 72 (26), 10194-10210). The scheme, directly from the compound of the formula (π), in the presence of a suitable range such as iota,8-diazabicyclo[5.4.0]~|-carbon-7-ene at a temperature ranging from 25 to 80C 'in a suitable solvent such as dimethylformamide' in the presence of a nucleophile of type (IV), using a benzotriazolyloxy-paraxyl (diammonium) scale such as hexafluoro-acid Obtained by appropriate activator treatment (II). Alternatively, the compound of formula (11) can be first converted to the formula by treatment (π) with a suitable gasifying agent such as gas oxidized scale (γ) or vaporized phosphorus (v) at a temperature ranging from 25 C to reflux. (ΠΙ) a gas-containing heteroaromatic compound. < (III) The compound can be subsequently carried out at a temperature ranging from ambient temperature to reflux in the presence of a base such as hydrazine, hydrazine, diisopropylethylamine or triethylamine, such as Λ/;#, • Conversion to a compound of formula (I) by reaction with a suitable nucleophile of the formula (ι), such as an amine, with or without the use of microwave radiation in a solvent of dimethylformamide, ethanol or tetrahydrofuran. In the specific case of ζ-NR=, the compound of the formula (1) can also be used in a range of, for example, at a temperature of, for example, a stilbene (diphenylmethylidene propylene) catalyst such as 2, lencyclohexyl In the presence of a phosphinyl)-li-dimethyl-linked alum-amine ligand, and in the presence of, for example, a third butyl group, a compound such as a soluble II (IV) ruthenium ui can be as shown in FIG. Instructions to get.

129 201130835 Figure 2 Using a dentate derivative of formula (VI) in a suitable solvent such as acetonitrile or propan-2-ol in the presence of, for example, sodium bicarbonate at temperatures ranging from ambient to reflux ( Wherein X = C1 or Br) treats the 2-amino hydrazine of formula (v) to produce the imidazole of formula (VII). Catalytic activity of a suitable catalyst such as ruthenium (di-based phosphine) or by acetic acid (Η)/triphenylphosphine under palladium catalyzed coupling conditions at a temperature in the range of 100-160 C The substance '(VII) is present in the presence of a base such as potassium acetate or potassium carbonate in a solvent such as dioxane, ethanol or dimethyl acetamide or a mixture thereof, with or without microwave irradiation. The compound is reacted with a gas derivative of the formula (VIII) to give a compound of the formula (Ιχ). In the specific case of R1() = Me, under reflux, in a suitable solvent such as acetonitrile, 'with suitable reagents such as those produced by the reaction of trimethyl decane chloride with sodium iodide' or under microwave heating in ethanol The methoxy derivative of formula (IX) is treated with potassium hydroxide to yield the desired compound of formula (Π). In the specific case of the formula (n) of 艮 = 1, 乂 = > 1 and y = cru, the sub-formula (ΙΙ-a) compound can be prepared by an alternative synthesis method as shown in Figure 3: σ 130 201130835

The imidazole of formula (X) [l, 2_al ambient temperature to reflux temperature, in the presence of H, a nitrile in the range of, for example, a suitable mixture of diterpene/water mixture, In the β Λ 9 face of the β Λ agent, 3-methoxy acrylonitrile. The 2-aminopyridine of the formula (V) was used. Formula ^ is converted to the corresponding formula (χι).,, Ho _ ^ ^ by the following. First by the temperature in the range 〇C to back k 'at the appropriate alcoholic age, with such as methanol or B-recording of the substrate is a matter of agreement, with: addition of ammonium sulfate or ammonium hydroxide; or by a range of 60. The mixture is refluxed: in a suitable solvent such as toluene, treated with a suitable Lewis acid such as trimethylaluminum, followed by ammonium chloride. The oxime of formula (XI) can be reacted with an unsaturated ester of formula (XII) wherein R 2 is 〇Η, -OMe, _〇Et or -NMe2 to give pyrimidine-4- of formula (Π-a) ketone. The 131 201130835 two =: garden, temperature to reflux temperature, in the presence of a suitable base such as ethanol or sodium sulphate, in a solvent such as ethanol, iso-tetragen (tetra) or water, with or without The specific trait of the formula (1) under the light wave of -C-〇Me and R9 = CF3 can be obtained by the formula (ΧΠΙ) 4_Fluorum whistling at ambient temperature 'in a suitable solvent such as ethanol (Ιν) It is obtained by treatment with a nucleophile such as an amine. 4_ Fluorine of formula (xm) can be made by the pulse of formula (XJ) at ambient temperature in the presence of a suitable base such as sodium hydroxide in a suitable solvent mixture such as a gas-burning/water 1,3,3,3-tetrafluoro-1-methoxy-2-(trifluoromethyl)propenene reaction to prepare, in another specific case, a compound of formula (Ib) (derived from (where X = N and Y = CRn ) can be obtained as illustrated in Figure 4:

OH C'-b) (XIV)

(lb) Figure 4 132 201130835 Treatment of a hydroxypyridone of the formula (Π-b) with a suitable gasifying agent such as phosphorus oxychloride (V) at a temperature ranging from 40 ° C to reflux to produce a formula (XIV) Dichloropyrimidine. The compound of the formula (XIV) can be reacted with boric acid of the formula (χν) under the Suzuki-Miyaura reaction conditions (Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457) to give the formula ( XVI) compound. The reaction can be in the range of 8 Torr. At a temperature to reflux, in a solvent such as 1,4-dioxane, in the presence of a base such as cesium carbonate, with or without the use of microwaves, such as by bis(diphenylphosphino) Suitable for palladium catalyst catalysis of a complex of ferrocene]dichloropalladium(II) and digas methane (1:1). The gas acridine of formula (XVI) can then be in a solvent such as dimethylformamide in the presence of a temperature ranging from ambient temperature to 120 ° C in the presence of, for example, MM-diisopropylethylamine. In the reaction with a nucleophile of the appropriate formula (IV), such as an amine, it is converted to a sub-compound. In another specific case, the sub-formula (I-c) compound (derived from formula (1), wherein X = N and Y = C-ORn) can be prepared as illustrated in Figure 5. 133 201130835

Figure 5 The dichloro derivative of formula (xiv) can be first used in the presence of a temperature ranging from ambient temperature to reflux in the presence of, for example, diisopropylethylamine or triethylamine. In a solvent of a base amide, ethanol or tetrahydroanion, it is converted into a compound of the formula (χνιι) by reaction with a nucleophile of the formula (IV). At a temperature of rc to ambient temperature, in a solvent such as tetrahydrofuran, a suitable base such as sodium hydride is used to treat the alcohol of the formula (χνιιι) to produce an ortho-oxy derivative which can be surrounded by The reaction with a chloropyrimidine of the formula (χνιι) in a suitable solvent such as tetrahydrofuran to produce a compound of the formula (I_C) or a sub-form of the compound of the formula (XIV) Reacts with an alkoxy derivative of an alcohol of formula (XVIII) from Street 134 201130835 to produce a compound of the formula (χιχ), followed by a temperature ranging from ambient to reflux, such as the condition #'-diisopropyl In the presence of a base such as an amine or triethylamine, a nucleophile of the appropriate formula (IV) is prepared in a solvent such as #,#, dimethyl carbamide, ethanol or tetrahydrofuran. In another specific case, the 'sub formula (Id) compound (derived from formula (1), wherein X di N and Y = C-NRmR! 5) can be prepared as shown in Figure 6:

(XXI) - (W) Figure 6 Reactive reaction of a dichloropyrimidine of formula (XIV) with an amine of formula (XX) in a solvent such as ethanol in the presence of a base such as triethylamine under reflux, 135 201130835 A compound of the formula (XXI). The compound of the formula (XXI) can be used in a solvent such as dimethylguanamine, ethanol or tetrahydrofuran in the presence of a base such as diisopropylethylamine or triethylamine at a temperature ranging from ambient temperature to reflux. In the reaction with a nucleophile of formula (IV), it is converted to a compound of formula (Id). Alternatively, the compound of formula (i-d) can be used, for example, in the presence of a temperature ranging from 60 to 140 ° C in the presence of, for example, ##-diisopropylethylamine or decyl carbonate, such as dimethylformamide Alternatively, the apyrimidine of the formula (XVII) can be treated with an amine of the formula (?) in a solvent of methylpyrrolidone with or without microwave irradiation. In other specific cases, compounds of the formula (1_6), (1_£'), (]^), and (1_11) (where X = Ν and Υ = C_CN, C_tetrazole, OCOOH, C-CONRmU, respectively) Prepared as illustrated in Figure 7:

136 201130835 In the range of 80 to 13 (rc temperature, in the case of such as 肆 (three stupid lining (0) silky, in the solvent such as bismuthamide, such as cyanide The cyanide ion source (11) is treated with a formula (fine) aergidine to obtain a cyano derivative of the formula (I_e). The nitrile of the formula (Ι-e) can be suitably used in a reflux such as f benzene. When the solution is converted into the sub-form (I_f), or in the (10) 4-base in a sealed S towel 'under microwave irradiation' in a solvent such as methanol/water, using a suitable processing method such as sodium hydroxide ( I_e) The substance 'produces the acid of the formula (I_g). The compound of the formula (I_g) can be used in the solvent of the formula (), such as the solvent, in the solvent In the presence of a plate, the indoleamine of the formula (Ih) is converted with an appropriate activation mechanism such as 1_p-benzobenzotrihydrate dimethylaminopropyl > AT-ethylcarbodiimide hydrochloride. The compound of formula (I) can be prepared via another synthetic route as shown in Figure 8.

In the presence of an isoproterenol such as α^λ^'-dimercaptoamine in the presence of isopropylethylamine in the presence of a temperature ranging from ambient temperature to reflux, The nucleophile of (IV) treats a bis-heteroaromatic compound of formula (?π) to yield a compound of formula (XXIII). At a temperature in the range of from 100 to 160 ° C, a suitable catalyst such as ruthenium (triphenylphosphine)palladium (ruthenium) or a catalytically active material produced from palladium(II) acetate/triphenylphosphine, such as potassium acetate, is used. Or a compound of the formula (ΧΧΠΙ) with the above formula in the presence of a base of potassium carbonate in a solvent such as dioxane, ethanol or dimethyl acetamide or a solvent mixture thereof with or without microwave irradiation VII) The intermediate reaction 'produces the desired compound of formula (I). In the specific case of the compound of the formula (I) wherein & or R9 is a halogen atom, further in the case of the eucalyptus-Miyazaki reaction conditions (Miyaura, N; Suzuki, A Chem. Rev. 1995, 95, 2457) with a suitable boric acid Or a boronate reaction to produce a compound of formula (I) wherein the corresponding halogen atom of R3 or R9 has been replaced by an aliphatic, aromatic or heteroaromatic residue. The reaction can be carried out in a solvent such as ruthenium (triphenylphosphine) palladium in a solvent such as 1,4-dioxane in the range of 8 〇 11 (at a temperature of rc) in the presence of a base such as potassium carbonate. Suitable for palladium catalyst catalysis. Alternatively, the compound of the formula amp) or R9 is a halogen atom may further react with a suitable amine in the presence of a palladium catalyst to produce a compound of formula (1) wherein the corresponding halogen atom of R9 has been replaced by an amine residue. The reaction can be carried out at a temperature of from 80 to 150 ° C in a solvent such as toluene, at the time of, for example, the third butt axis, under the use of or without the ride, by the generation of ## The benzylideneacetone) two (9) and biphenyl-2-yl-dibutyl butyl scales are suitable for catalyzing the catalyst. In another specific case, the compound of formula (1) wherein % is a hydrogen atom can be further reacted by treatment with a halogenating agent such as succinimide or molecular bromine in a solvent such as acetic acid or dimethylformamide. A compound of formula (I) wherein R9 is now a halogen residue. In another specific case, the compound of formula (1) wherein Z = NR5_a_R5 is an argon atom may be further reacted with a suitable base such as sodium hydride in a solvent such as dimethylformamide, followed by a range of 0 to reflux. Adding an alkylating agent such as mothane to give Rs is now an alkyl group (G compound. In another special case 'R6, R7, r8, r94 R丨1 (in Y=CR) The residue portion of the specific case of 1 contains a formula of an amine moiety functionalized with a suitable protecting group such as tributyl carbonyl (BOC), benzyloxycarbonyl (CBZ) or p-methoxybenzyl (PMB). ()) The compound can be removed under standard conditions (Protective Groups in Organic Synthesis, ISBN 0471697540). The corresponding free amine can then be further functionalized under standard conditions to yield the corresponding guanamine. Amines, ureas and oxime alkylated and arylated amines. In another particular case, the residue of the particular case contains a compound of formula (I) which is functionalized with a suitable protecting group such as a methyl ester. Available in standard conditions Protective Groups in Organic Synthesis, ISBN: 0471697540) The protecting group of the citric acid moiety is removed. The corresponding formic acid can then be further functionalized under standard conditions to yield the corresponding guanamine. In another specific case, a compound of formula (!) wherein the residue of R9 is a nitro moiety can be used, for example, in a solvent such as 139 201130835 in a solvent such as ethanol at a temperature in the range of 2 〇 1 Torr (rc). Treatment of tin (II) with a suitable reducing agent, using a suitable catalyst such as palladium on carbon or platinum/carbon, ambient temperature or methanol age of dissolution 'at atmospheric pressure hydrogen to reduce to phase such as ethylamine [Embodiment] The compounds of the present invention and the intermediates therefor are provided by the following examples (10) 6) (including preparation examples (preparation of state mouth = and in the order of - (iv) to provide a complete and complete approach to the skilled person) The explanation of the present invention is not to be construed as limiting the scope of the subject matter, as set forth in the previous section of the description. Soil Preparation 1 Miso and [l,2-a]pyridin-6-carbonitrile H2n

Use 5 〇% 2-chloroethane aqueous solution (26 4 ml, 21 〇 milli 6 6 amine based on the test nitrile (10 gram, 8 〇 millimol) B guess (10) ear ml) ίί reduction gift. After 6 hours, the mixture was cooled to the veins. Concentrate the mixture to a low volume (about (10) ml) aqueous solution of sodium hydride to a neutral pH value, and take a B-toothed sputum. The value is obtained by digesting with methane (2 x 300 ml). The title compound (22.54 g, 94%) was obtained eluted eluted The seat is in the second color 140 201130835 LRMS (m/z): 144 (M+l)+. ^-NMR δ (CDC13): 7.29 (dd, 1H), 7.71 (d, 1H), 7.73 (d, 1H), 7.80 (d, 1H), 8.61 - 8.62 (m, 1H). Preparation of 2 6-fluoro-salt and [l,2-d] ° bite

A brown solid (93%) was obtained from 5-fluoropyridin-2-amine and 2-hexanes acetaldehyde (50% aqueous). LRMS (m/z): 137 (M+l)+. ^-NMR δ (CDC13): 7.12 (m, 1H), 7.57 - 7.67 (m, 2H), 7.70 (bs, 1H), 8.04 - 8.13 (m, 1H). Preparation of 3 6-azamidazo[1,2-fl]pyridinium

Obtained as a brown solid (71%) from 5-chloropyridin-2-amine and 2-chloroacetaldehyde (50% aqueous), followed by flash chromatography (1:1). The crude product was purified by calcination / ethyl acetate. 141 201130835 LRMS (m/z): 153 (M+l)+. ^-NMR δ (CDC13): 7.13 (d, 1H), 7.53 - 7.60 (m, 2H), 7.66 (s, 1H), 8.18 (s, 1H). ''' Preparation of 4- 3-(4-pyridyl-2-yl) miso and [i,2_a]pyrene than bite-6-carbonitrile

a) 3-(4-methoxypyrimidin-2-yl)imidazolium iia]pyridine_6 carbonitrile in a microwave oven 'buffering nitrogen to agitated 2_gas_4_methoxypyridine (1.14 Muke's 7.9 mM), Mww and carbonitrile (preparation of 0.75 g, 5.2 mmol), potassium carbonate (! 45 g, 1 〇 5 mmol) and triphenylphosphine (0.55 g) , millimeters)! 4_ 2 gauge (1G ml) and 5 points of acetic acid (5 ml) in the acetic acid peak) (0.24 g, u millimoles)

The OH was irradiated by the microwave for 2 hours. The test product was re-equilibrated under the same conditions for 6 times and the solvent was evaporated. The residue was dissolved. The mixture was separated from water and taken up to remove insoluble black solid ethyl acetate and extracted with 2 M aqueous hydrochloric acid (X 8 g).

The value reached approximately '6 body Wei Qian treatment until the solid formed by PH k de and was in the vacuum medium batch of the title compound (2 65 g). Treat the secret black solid with 2 Μ hydrochloric acid aqueous solution (2 cis 142 201130835, liter) And thief. (4) Body carbon = liquid, PH value up to _ 6. The solid formed by the rhyme and in the true = 匕, 乂, produced the first batch of the title compound (〇 77 grams) grams (43%). όΛΖ LRMS (m / z): 252 (M+l)+ 〇^-NMR δ (DMSO-^): 4.08 (s, 3H), 6.88 (d 1H) 7 7, (^^), 7.95^^8.63 (,1^8.67 (^ b) 3-(4-Pyrylpyrimidin-2-yl) oxazolo, 2_a] 唆 _6 • A production of sodium (H. 8 g, 78.6 mmol) added to Lai Yue悬浮(4_Methoxypyrimidin-2-yl)imidazo[丨,2_a]pyridine_6_曱^ '3.3 g '13" millimolar in acetonitrile (135 ml) suspension. ~ Aerated triterpenoids (9.9 ml, then millimolar) and 80 in the sealed tube. (The mixture was heated for 24 hours, then cooled to ambient temperature. The solvent was removed under reduced pressure and the residue was suspended in water. A saturated aqueous sodium thiosulfate solution was added until the dark color subsided and formed a pale brown solid. The title compound (3 2 g, 99%) was obtained as a pale brown solid.</RTI> <RTI ID=0.0></RTI> <RTIgt; (M-1). ^-NMR δ (DMSO-i/6): 6.42 (d, 1H), 7.82 (d, 1H), 7.97 ' (d,1H), 8.27 (d,1H), 8.78 ( s,1H), 10.43 (s;lH). Preparation 5 3·{4-[(3 and)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2峋pyrr$- 6-carbonitrile 143 201130835

NH2

r 0 hexa- 1 acid (benzotrienylpyroxy) ginseng (dimethylamino)H^CGl^39 mM) and 1,8-diazabicyclo[5.4.〇] 十反- Alkene (0.187 ml, 丨.25 mmol) was added to the stirred 3, base-2-yl) flavored saliva and (10) bite each of the guesses (prepared, 〇2 〇.84 mmol) In a solution of dimethyl decylamine (3 ml). After 15 minutes of mixing at ambient temperature, (3i?)_3_amine-based slightly biting formic acid tert-butylate (〇.418 g, 2 G9 mmol) was added dropwise and the mixture was stirred at ambient temperature for a further 16 hours. After adding water and extracting with ethyl acetate, the organic layer was washed with water, 4% aqueous sodium hydrogen carbonate, brine, dried (MgSO.sub.4) and evaporated. The title compound (7 %) was obtained as a yellow solid. LRMS (m/z): 420 (M+l)+. H-NMR &quot;δ (DMSO-i^): 0.92 _ 1.65 (m, 15H) 3 66... 4.04 (m, 3H), 6.29 - 6.69 (m, 1H), 7.91 (d, 2H), 8.12 _ 8 33 (m, 1H), 8.40 - 8.68 (m, 1H), 10.28 - 10.61 (m, 1H). b) 3-{4-[(3Λ)-Brigade bite ·3·ylamino] spray bite _2_ base} taste jun and 144 201130835 〇 bite -6-carbonitrile will be fluoride, (1, 〇 ML, millimolar (10)-3-{[2-(6·cyano-sodium-like-salt and kiss-like, drop-by-drop, add to the small formic acid tert-butyl 5 (preparation 5a, 0.25 octahidine) a solution of methylene chloride (5 ml) in a solution of hexanes (5 ml). After completion of the reaction, water was added and the solid compound i was then extracted with dichlorohydrazine. Drying (MgS〇4) The organic layer was purified by flash chromatography (EtOAc: EtOAc: EtOAc) +l) + W-NMR δ (DMSO-Can 1.08 - L87 (m, 4H), 2 〇 1H), 2·55 - 3.35 (m, 4H), 4.13 (bs, 1H), 6 45 (d, 1H) 7 ' 7.79 (m, 2H), 7.91 (d, 1H), 8.21 (bs, 1H), 8 j5 (bs· -10.44 (bs, 1H). ' λ Preparation 6 (J?)-3-( 4-(methyl(piperidin-3-yl)amino)pyrimidine:yl)imidazo[1,2-a]B than bite-6-

a) 3-[[2-(6-Cyano-l,8a-dihydromylon and [i,2.fl]n-pyridyl)-l-propyl-4-yl](methyl)amino]piperidin Pyridin-1-carboxylic acid tert-butyl ester 145 201130835 Sodium (60% mineral oil dispersion, 〇31 g, 7 mAh =) Knife batch added (8) MW cyano miso and pyridoxine Piperidinic acid citrate third butyl (preparation 5a, gram, 9 mM) of dimethyl ketoamine (i5 ml) Γ7: when stalk two air precipitates have stopped, 'add iodomethane (0.48 ml, in The reaction mixture was allowed to be applied overnight at ambient temperature. The agent was removed and the residue was partitioned between acetic acid W and water = layer, and by reverse phase chromatography (from water hydrazine hydrated water / 1:1 acetonitrile - Methanol as a dissolving lysate 01% v/v methyl I buffer] 0% to 100%) purified residue compound (G.26 g, 16%). LRMS (m/z): 434 (M) +l)+. Η4^64=·89(ΐη,1Η), 3.〇9〇&quot;,3Η),4.18^,2Η),6.41- ΓΐΗ; 〇;w,〇(dd,1HX7^ (bs ,1Η),10.55 (bs,1Η) b) W-3-(4·(methyl(Big _3·yl)amine)))) (10) [l,2-a] 6-carbonitrile according to the experiment as described in Preparation 5b Order, _ ((2 gas-based base bite and [U♦ than bite _3 · fine bit I base) (methyl) amine) (d) small butyric acid dibutyl ester (preparation 6a) to obtain a solid (6 〇 0 / 〇). LRMS (m/z): 334 (M+l)+. Preparation 7 3-{4-'-Bite _3_ylamino group] biting _2 group} miso and order pyrene 146 201130835 唆_6_甲猜

a) (35)-3·{[2-(6-Cyanoimidazo[L2 but pyridyl_3_yl)-crossed 4-yl]amino}piperidin-1-carboxamidine tert-butyl ester' As described in the preparation of the experimental procedure described in 5a, consisting of 3_(4-hydroxyl-injection•2_yl)isoxazo[l,2-a]«-pyridinonitrile (prepared as well as (3 external 3-methylpiperidine- 1-Dicarboxylic acid tert-butyl ester obtained a brown solid (66%). After the reaction was completed, the mixture was partitioned between water and ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogen carbonate, brine, and dried (MgS04) The residue was purified by flash chromatography (yield: EtOAc: EtOAc: EtOAc: EtOAc: 1.60 (s,9H), 6.30 (d,1H), 7.41 (d 1H), 7.78 (d,1H), 8.30 (d,1H), 8.61 (s,1H),10.55 (s,1H)., b 3-{4-[(35)-Big -3-amino-amino] 嚷 _2 - _2 [ 124 [124 pyridine-6-carbonitrile is not photographed as described in Preparation 5b, By (3 about -3-{[2-(6-cyanopyrano[1,2-&lt;7]*» than -3-yl) cancer biting-4-yl]amino} π 辰 bite 1-butylic acid tert-butyl ester (Preparation 7a) gave a solid (98%). LRMS (m/z): 320 (M+l) + 147 201130835 H-NMR δ (CDC13): 2.91 (s, 2H), 3.23 (dt, 1H), 5.70 (s, 1H), 6.40 - 6.12 (m, 1H), 7.45 - 7.30 (m, 1H), 7.88 - 7.67 (m5 1H), 8.25 (s , 1H), 8 59 (d, 1H), 1〇55 (s, m). Preparation 8 2-(6·fluoroimidazo[1,2_α]βpyridinyl)pyrimidine·4-alcohol

a) 6-fluoro-3-(4-methoxyindole-2-yl) miso and [1,2-(|]° ratio bite according to the experimental procedure as described in Preparation 4a, 2-Chlorine -4-曱oxycarcinoma bite (7.0 g, 48 mmol) reacted with 6-fluoroimibene [i,2-a]n bite (preparation 2, 4.40 g, 32 mmol). Ethyl ester was added to the crude reaction mixture and the suspension was filtered through Celite®. The filtrate was washed with water and extracted several times with 2 hr of aqueous hydrochloric acid. The combined aqueous layer was washed with diethyl ether and then neutralized with aqueous sodium hydroxide. The product was extracted with EtOAc (m/z) (m/z). !H-NMR δ (CDC13): 4.11 (S, 3H), 6.58 (d, 1H), 7.60 (q, 1H), 7.71 (dd, 1H), 8.49 (d, 1H), 8.61 (s, 1H) , 9.98 (dd, 1H) = b ) 2-(6-fluoro miso and [ι, 2_α] β ratio bite _3_ base) mouth bite _4_ alcohol to 6-fluoro_3-(4-曱 oxygen Addition of 35% potassium hydroxide to a solution of chloropyrimidin-2-yl)imidazo[l,2-a]pyridine (manufactured 148 201130835 for 8a '1.5 g '6.1 mmol) in ethanol (ι) Solution (9.8 ml, 61.3 mmol). The reaction mixture was subjected to 120. (: microwave irradiation for 1 hour. The organic solvent was removed under reduced pressure and the aqueous phase was neutralized with 5 Μ hydrochloric acid. The precipitate was filtered, washed with water and dried. The title compound (7 〇〇/0) was obtained as a white solid, which was used without further purification. LRMS (m/z): 231 (M+l)+.]H-NMR δ (DMSO-J6) ): 6.31 (s, 1H), 7.77 (d, 1H), 8.17 (s, 1H), 8.73 (bs, 1H), 9.94 (bs, 1H), 12.75 (s, 1H). Preparation 9 (Λ)· 2-(6·Fluor taste and [m]*·Bite _3_ base)_N-(Budden base) acridinium-4-amine

a) (3 and)·3-({[2_(6_fluoroindole[1,2_«]«» bite each base) bite _4_ base]oxy}amine) brigade bite-1- Tert-butyl formate according to the experimental procedure as described in Preparation 5a, from 2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidin-4-ol (Preparation 8b) and (/ ?)·3·Aminopiperidine-1-carboxylic acid tert-butyl ester gave a yellow solid (65%). By reverse phase chromatography (from Waters C-18 to oxidized stone, water / 1:1 acetonitrile _ sterol as solvent 149 201130835 [0.1% v/v formic acid buffer] 0% to 100%) The crude product was purified. LRMS (m/z): 413 (M+l)+. ^-NMR δ (CDC13): 1.44 (s, 9H), 2.13 - 1.53 (m, 4H), 3.65 - 3.23 (m, 4H), 5.14 (s, 1H), 6.24 (d, 1H), 7.23 (ddd , 1H), 7.68 (dd, 1H), 8.27 (d, 1H), 8.54 (s, 1H), 9.99 (s, 1H). b) (i〇_2-(6-fluoroimidazo[1,2-a]"pyridin-3-yl)-N-(piperidin-3-yl)pyrimidin-4-amine as described in Preparation 5b The experimental procedure consists of 〇R)-3-(2-(6-fluoroimi-α sitting and [1,2-a]ntb bit-3-yl) mouth. 1,4--4-amino group) bite-1 -carboxylic acid dibutyl hydrazine (Preparation 9a) gave a yellow solid (70%). LRMS (m/z): 313 (M+l)+. ^-NMR δ (CDC13): L65 (dd, 2H), 1.90 - 1.71 (m, 3H), 2.00 - 1.89 (m, 2H), 2.88 (d, 3H), 5.57 (d, 1H), 6.22 (d , 1H), 7.22 (ddd, 1H), 7.66 (dd, 1H), 8.22 (d, 1H), 8.53 (s, 1H), 9.98 (dd, 1H). Preparation 10 1-{[2-((3Λ)-3-{[2-(6-fluoroimidazo[l,2-fl]pyridin-3-yl)pyrimidin-4-yl]amino}piperidine- 1-yl)-2-mercaptopropyl]oxy}&quot;bipiridine-2,5-dione

150 201130835 a) 2-((3Λ)-3-{[2_(6-1 Imidazo[ι,2·α]»bipyridin-3-yl)-anthran-4-yl]amino} brigade bite- 1_yl)-2-methylpropionic acid methyl vinegar stirred (8)-2-(6-denimidazo[i,2_a]pyridine-3-yl)_ν-(Nylidene-3-yl)pyrimidin-4-amine (Preparation of % ' 〇10 〇g, 〇32 mmol), 2 bromo-2-propionic acid ethyl ester (0.137 g, 〇.7 〇 millimolar) and potassium carbonate (0.066 g, 0.48 mmol) A solution in dimercaptocaramine (丨 ml) and heated to 80. (: After 16 hours, add water to the reaction mixture and extract the mixture with a gas purge. Dry (MgS04) organic layer and evaporate by reverse phase chromatography (from Waters C_18 cerium oxide, water / 1 :1 acetonitrile-nonanol as a dissolving agent [by 〇.l 〇 / ov / v 曱 缓冲 〇 〇 〇 至 至 至 至 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 66 66 66 66 66 66 %) LRMS (m/z): 413 (M+l)+. b) 2-((3i?)-3-{[2-(6-fluoroimidazo[ι,2-α]acridine- 3-yl)bite-4-yl I-amino}Nanden-1-yl)_2-methylpropionic acid Potassium hydroxide (0.028 g, 0.42 mmol) was added to the stirred (8)-2-( 3-(2-(6-fluoroimidazo[1,2-a] π-pyridyl-3·yl)-paste _4_ylamino)tripridin-1-yl)-2-methylpropanoate Ester (preparation 10a, 〇〇9 〇g, 〇21 mmol) in methanol (1 mL). The reaction mixture was stirred overnight at room temperature, then heated to 50 ° C and stirred for additional 24 hours. The mixture was neutralized with 2 M aqueous hydrochloric acid/salt, followed by extraction with a gas. The organic layer was dried <RTI ID=0.0>(M </RTI> <RTIgt; </RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> <RTIgt; LRMS (m/z): 399 (M+l)+. c) [{[2_((3 and)·3·{[2_(6-fluoroimidazo[l,2-ii]pyridyl)) shouting 151 201130835 _4_ base] amine base} bite -1- N-hydroxybutaneimine (0.016 g, 0.14 mmol) and 1,3-diisopropyl Carbodiimide (0.022 ml, 0.14 mmol) was added to the cooled (ice bath) and stirred (and) 2 - (3-(2-(6-gas imi) [1,2_bipyridine- 3_yl) pyridine _4·ylamino)piperidinyl)_2_mercapto acid (preparation 10b, 0.050 g, 0.13 mmol) of tv, dimethylformamide (1 ml) In solution. After stirring overnight at ambient temperature, water was added to the reaction/tt* compound and the mixture was burned with a gas. The organic layer was dried (M.sub.4) and evaporated to give the crude title compound (m. LRMS (m/z): 496 (M+l)+. Preparation 11 (Λ)_2_(6-fluoroimidazo[l,2-a]pyridin-3-yl)-N-methyl-N-(piperidin-3-yl)pyrimidine-4-amine

a) (Λ)_3·((2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-yl)(methyl)amino)piperidine_1·carboxylic acid Tributyl ester according to the experimental procedure as described in Preparation 6a's (3 magic-3-({[2-(6- 152 201130835 rat taste σ sitting and [1,2-ύΓ]β ratio bit-3-yl) ) is obtained by trimethyl butyl benzoate (preparation 9a) and methyl iodide. Purification by flash chromatography (0-100% ethyl acetate in hexane) The title compound (0.52 g, 55%), mp. 1.67 (bs, 1H), \j2 -1.93 (m, 2H), 1.95 - 2.05 (m, 2H), 2.68 (bs, 2H), 2.65 - 2.88 (m, 2H), 3.07 (s, 3H), 6.37 (d,1H), 7.17 - 7.26 (m,1H), 7.68 (dd, 1H), 8.31 (d, 1H), 8.54 (s, 1H), 9.96 (dd, 1H) b) (and) -2- (6-fluoroimidazo[1,2-a]°pyridin-3-ylmethyl-yi (Bistidyl-3-yl)pyrimidin-4-amine according to the experimental procedure as described in Preparation 5b, i?)-3-((2_(6-azamidazo[l,2-a]pyridin-3-yl))) (meth)amino) (n-butyl citrate) 11a) Obtained a solid (51%). Reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 acetonitrile-methanol as a dissolving agent [0.1% v/v citric acid buffer] 0% to 1%) to purify the crude product LRMS (m/z): 327 (M+l)+.]H-NMR δ (CDC13): 1.60 - 2.02 (m, 6H), 2.58 (td, 13⁄4) 2.79 (t, 1H), 3.04 (s , 3H), 3.13 (t, 1H), 5.30 (s, 1H), 6.33 (d^ 1H), 7.22 (ddd, 1H), 7.67 (dd, 1H), 8.27 (d, 1H), 8.54 (s, 13⁄4) 9.98 (ddd, 1H)' ' Preparation 12 iV-ethyl-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-#-[(from)-leer beer-3 -yl]pyrimidine-4-amine 153 201130835

a) (Λ)-3-(ethyl (2_(6-fluoroisobenzopyrene)) acridinyl-4-yl)amino)piperidine-1-carboxylic acid tert-butyl ester according to preparation 6a The experimental procedure described in the third step consisting of (3[3_(6_fluoroimidazo[1,2-α]pyridine-3-yl)pyrimidinyloxyamino)piperidinecarboxylic acid The ester (Preparation 9a) and ethyl iodide afforded a white solid (yield: 58%). The crude product was purified by flash chromatography (9:1 hexane methane / decyl alcohol) LRMS (m/z): 441 (M+l) +. b) Ethyl 2-(6-fluoroimidazolium 丨, 2_ίΐ)pyridin-3-yl)-#-[(3 and)-Nandidyl-3-yl] 唆4·amine As in the experimental procedure described in Preparation 5b, from (and)-3-(ethyl(2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidin-4-yl)amino Piperidine-1-carboxylic acid tert-butyl ester (Preparation 12a) gave a solid (100%). LRMS (m/z): 341 (M+l)+. Preparation 13 batches (cyclopropylmethyl)-2·(6-fluoro%oxazolo[1,2-α]pyridine_3_yl HV-[(3J?)-piperidin-3-yl]pyrimidine-4-amine 154 201130835

a) (3J?)-3-{(cyclopropylmethyl)[2_(6_fluoroimidazo[12 small pyridine base] mouth bite-4-yl] amine 丨 brigade bite small formic acid third vinegar According to the experimental procedure as described in Preparation 6a, from (3^_3_g[2-(6-敦°米哇和[1,2-外比咬-3-yl)pyrimidinyl]oxy}amino group The n-butyl benzoate (preparation 9a) and (bromomethyl)cyclopropane gave a white solid (47%). The crude product was purified by flash chromatography (92:8 dioxane / methanol). LRMS (m/z): 467 (M+l)+. !H-NMR δ (CDC13): 0.39 (bs, 2H), 0.64 (bs, 2H), 1.12 (bs, 1H), 1.46 (bs, 3H), 1.60 (bs, 6H), 1.87 (bs, 2H) , 2.06 (bs, 2H), 2.68 (bs, 1H), 2.88 (bs, 1H), 3.37 (bs, 1H), 3.55 (bs, 2H), 4.02 - 4.43 (m, 2H), 6.48 (bs, 1H ), 7.22 (bs, 1H), 7.68 (bs, 1H), 8.30 (bs, 1H), 8.53 (bs, 1H), 10.01 (bs, 1H) b ) Λ4cyclopropylmethyl)-2-(6- Flumimidazo[1,2_中比pyridine·3·yl)Good [(3 and)-Brigade bite_3_yl] mouth bite-4-amine according to the experimental procedure as described in Preparation 5b, by (3 And)_3_{(cyclopropanyl)[2_(6_fluoroisoxazo[i,2_fl]nbidin-3-yl)pyrimidinylamino]amino}α-pyridin-1-decanoic acid tertidine The ester (Preparation 13a) gave a solid (85 〇 / 〇). LRMS (m/z): 367 (M+l)+. ^-NMR δ (CDC13): 0.39 (d, 2H), 0.63 (d, 2H), 1.12 (bs, 155 201130835 1H), 1.74 - 1.94 (m, 2H), 2.03 (bs, 2H), 2.53 - 2.63 (m,1H) 2.81 (t, 2H), 3.06 - 3.25 (m, 3H), 3.39 (bs, 2H), 3.47 (bSj 2H) 6.44 (d,1H), 7.23 (ddd,1H), 7.68 (dd,1H), 8.27 (d,1H)' 8.53 (s, 1H), 10.02 (dd, 1H) ' Preparation 14 2·Imidazo[1,2-α]pyridin-3-ylpyrimidin-4-ol

0 pi°

a) 3-(4-Methoxypyrimidin-2-yl)imidazo[l,2-a]pyridylpyrimidine according to the experimental procedure as described in Preparation 4a, from 2-ox-4-pyroxypyrimidine And imidazo[1,2-[beta]]pyridine gave an off-white solid (39%). LRMS (m/z): 227 (M+l)+. JH-NMR δ (DMSO-i/6): 4.12 (s, 3H), 6.84 (d, lH)s 7 26 (t,1H), 7.57-7.50 (m,1H), 7.83 (dd,1H), 8·56 (s,1H),8 65 (dd, 1H), 9.93 (dd, 1H) ° b) 2-imidazo[l,2-fl]pyridin-3-ylpyrimidin-4-ol at 100° The stirred 3-(4-methoxypyrimidinyl)imidazo[l,2-a]acridine (preparation 14a, 0.38 g '1.7 mmol) and 48% aqueous hydrogen bromide (25) a mixture of milliliters). After 3 hours, the solvent was evaporated and the residue was treated with isopropyl alcohol. The solid was collected by filtration and dried <RTI ID=0.0> LRMS (m/z): 213 (M+l)+. H-NMR δ (DMSO-i/6): 6.63 (d, 1H), 7.66 (t, 1H), 8.13 -8.00 (m, 2H), 8.42 (bs, 1H), 8.96 (s, 1H), l 〇.i6 (d, 1H) 〇Preparation of 15 , 2-Ga-5-fluoro-4-methoxypyrimidine

a) 2,4-dioxa-5-fluoropyrimidine to a stirred 5-fluoropyrimidine·2,4(1Η,3Η)-dione (3.0 g, 23 mmol) and five gasified phosphorus (14.41 g) Chlorolyte _ (12. 6 ml '13 〇 millimolar) was added to the mixture of 69 mmol. The reaction mixture was heated to reflux, stirred for 5 hours, then cooled to ambient temperature and stirred. The mixture was carefully poured onto ice/water (6 mL) and mixed for 1 hour. Sodium vaporate was added and the product was extracted with dioxane. The title compound (84%) was obtained as a yellow solid. LRMS (m/z): 167 (M+l)+. 'H-NMR δ (CDC13)· 8.49 (s, 13⁄4) b) 2-Ga-5-fluoro-4-methoxypyrimidine was added in portions (0.45 g, 19.6 mmol) to methanol (2 〇) Σις中. After all the sodium has reacted, add 2,4·2 gas _5_ 咬 啶 ( (made a, 3.25 grams ' 19.5 millimoles) of sterol (1 () ml) solution 157 201130835 and around f The fresh mixture was stirred overnight. The mixture was diluted with EtOAc (EtOAc m. %), which can be used without further purification. LRMS (m/z): 163 (M+l) + 〇^-NMR δ (CDC13): 4.11 (s, 3H), 8.20 (d, 1H) Preparation 16 5-fluoro-2-(6-fluoroimidazo[ijw]pyridine-3-yl)pyrimidine-4-ol

a) 6·fluoro-3·(5-fluoro-4-methoxypyrimidin-2-yl)imidazopyridine pyridine 2_chloro_5_fluoro_4_曱 according to the experimental procedure as described in Preparation 4a The oxypyrimidine (Preparation 15b, 1.1 Torr, 6.8 mmol) was reacted with 6-fluoroimidazo[l,2-a]pyridine (Preparation 2, 13 gram '95 mM). The crude product was purified by flash chromatography eluting elut elut elut elut elut elut elut LRMS (m/z): 263 (M+l)+. !H-NMR δ (CDC13): 4.21 (s, 3H), 7.11 (ddd, 1H), 7.28 (dd, 1H), 8.38 (d, 1H), 8.53 (s, 1H), 9.87 (dd, 1H) b) 5_Fluorofluoromiso and [l,2_&lt;i]e than bite_3_yl) mouth bite alcohol to 6-fluoro-3-(5-fluoro-4-methoxypyrimidin-2-yl) Isocarbazide [Ha] pyridine 158 201130835 (preparation, 200 mg, 0.76 mmol) of ethanol, medium 5% potassium hydroxide aqueous solution αι liter) &gt; Valley The reaction mixture was subjected to a shoe microwave fine hour. ^莫耳耳) Two = and 'then neutralized with 5 Μ hydrochloric acid: The filtrate was evaporated to dryness. The mixture was triturated with several portions of EtOAc/MeOH. LRMS (m/z): 249 (M+l)+. Preparation 17 W_5-1 -2-(6-Fluoroindole: bit): Ν ( ((Bucking · 3_) pyrimidine-4-amine

a) (Λ)_3·(5·Fluor-2·(6-fluoroimithia[1,2-a]” is more than -3-yl) oxime-4-ylamino) The third butyl citrate was prepared according to the experimental procedure as described in Preparation 5a, from 5-fluoro-2-(6-fluorophenophenone[1,2_a]n-pyridylpyrimidin-4-ol (Preparation 16b) And (8)·3 aminyl hydrazine-1-carboxylic acid tert-butyl ester gave a solid (22 〇 / 〇). The crude product was purified by flash chromatography (9:1 dioxane / methanol). z): 431 (M+l)+ 159 201130835 b ) (Λ)_5-fluoro-2-(6-fluoroimidazo[l,2-a]»pyridin-3-yl)_N-(piperidine- 3-yl) octyl-4-amine according to the experimental procedure as described in Preparation 5b, (X-fluoro-2-(6-fluoroimidazo[l,2-a]pyridine-3) - Benzylpyrimidin-4-ylamino)piperidine-1-furic acid tert-butyl ester (Preparation 17a) gave a solid (100%). LRMS (m/z): 331 (M+l)+. 2-ox-4-methoxy-5-methylpyrimidine

A white solid (100%) was obtained from 2,4-dioxa-5-mercaptopyrimidine and sodium methoxide according to the procedure procedure as described in Preparation 15b. LRMS (m/z): 159 (M+l)+. H-NMR δ (CDC13): 2.12 (d, 3H), 4.03 (s, 3H), 8.10 (d, 1H) Preparation 19 2-(6-fluoroimidazo[1,2-ίφ-pyridin-3- 5-methylpyrimidin-4-ol

160 201130835 pyridine a) 6-fluoro·3-(4-methoxy-5-methyl-hydroxy-2-yl) and [ι2_α] according to the experimental procedure as described in the injury 4a _5·methyl Spray bite (preparation 18, 1.70 grams, 10.7 millimoles) on the shore. Purification of the crude material by reverse phase chromatography (from Waters (4) dioxo, = acetonitrile acetal [passage. 1% v/v formic acid buffer] 0% to _) yielded a white solid The title compound (24%). LRMS (m/z): 259 (M+l) + 〇H NMR δ (CDC13): 2.18 (s, 3H), 4.12 (s, 3H), 7.24 (dd, 1H), 7.64 - 7.72 (m, iH ), 8.29 (d, 1H), 8.55 (s, 1H), 9.95 (dt, b) 2-(6-Fluoro # and called small bite _3 base) · 5 methyl squid glycol according to preparation 16b In the experimental procedure described, 6-gas each (4_methoxy_5_曱基钱·2_ base) and H&lt;(Preparation 19&amp;, 〇45 g, 1.7 mmol) and A 35% aqueous potassium hydroxide solution (2 79 mL, 17.4 mmol) was reacted. The reaction was concentrated in vacuo and water was added. The title compound (100%;) was obtained as a white solid. LRMS (m/z): 243 (M-l)+. lR NMR 6 (DMSO-^): 3.33 (s, 3 Η), 7.60 - 7.66 (m, 1 Η), 7.87 (dd,, 1 Η), 8.03 (brs, 1 H), 8.72 (s, 1 H ), 9.91 (bs, 1 H). Preparation 20 161 201130835 2-(6-fluoroimidazo[l,2-fl]pyridin-3-yl)-5-methyl-7V-[(3 and)-piperidin-3-yl] mouth-changing-4 -amine

a) (3/?)-3-{[2_(6-fluoroimidazo[1,2-α]"pyridin-3-yl)-5-methylpyrimidin-4-yl]amino}piperidine 1-butylic acid tert-butyl ester according to the experimental procedure as described in Preparation 5a, from 2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-5-mercaptopyrimidine-4 - Alcohol (Preparation 19b) and (Λ)-3-Aminopiperidine-1 -decanoic acid tert-butyl ester afforded a pale yellow solid (35%). The crude product was purified by flash chromatography (9:1 dioxane / methanol). LRMS (m/z): 427 (M+l)+. !H-NMR δ (CDC13): 1.51 (bs, 2H), 1.72 (bs, 9H), 2.01 -2.29 (m, 5H), 3.42 (bs, 1H), 3.56 - 3.83 (m, 3H), 4.37 ( Bs, 1H), 7.27 (bs, 1H), 7.73 (bs, 1H), 8.13 (bs, 1H), 8.57 (bs, 1H), 10.02 (bs, 1H) b) 2_(6_fluoroimidazolium &quot; Bispin-3-yl)-5-methyl-7V-[(3i?)-piperidin-3-yl]pyrimidin-4-amine according to the experimental procedure as described in Preparation 5b, from (3 and)- 3-{[2-(6-gas 13 m σ sita[l,2-i3]ntbn--3-yl)-5-fluorenyl-t-butyl-4-yl]amino-l-carboxylic acid Butyl ester (Preparation 20a) gave a white solid (70%). 162 201130835 LRMS (m/z): 327 (M+l)+. ^-NMR δ (CDC13): 1.69 (bs, 3H), 1.74 - 2.04 (m, 4H), 2.87 (bs, 1H), 3.21 (bs, 3H), 4.35 (bs, 1H), 5.23 (bs, 1H) ), 7.21 (bs, 1H), 7.66 (bs, 1H), 8.05 (bs, 1H), 8.50 (s 1H), 9.99 (bs, 1H) ' Preparation 21 2-(6-fluoroimidazopyridine-3_ Pyridoxine-3-ylpyrimidin-4-amine

a) 3_{[2-(6-fluoroimidazopyrenepyridin-3-yl)octidine-4-ylguanidino} 0 pirate-1-carboxylic acid tert-butyl as described in Preparation 5a The experimental procedure consists of 2 scented [l, 2-a] broken -3: base) spray bite (preparation (6) and w_3 amine group. (μ%) by reverse phase chromatography (C-l8 dioxo from Waters, water / 1:1 acetonitrile as dissolving [0.1% v/v formic acid buffer] 〇0/〇 to 1〇 〇V〇) Purified crude product LRMS (m/z): 399 (M+l)+. b) 2-(6-fluoroimidazolium-pyridylpyridinium-3-yl)pyrrolidinyl-pyrimidine 163 201130835 as prepared The experimental procedure described in 5b consists of 3_{[2·(6-fluoroimidazo[1,2-α]pyridin-3-yl)caridin-4-yl]amino}pyrrolidine 4•carboxylic acid tert-butyl The ester (Preparation 21a) gave an oil (77%). – LRMS (m/z): 299 (M+l)+. !H-NMR δ (CDC13): 0.83 - 0.98 (m, 1H)} 1.82 (ddd, 1H), _ 3.34 (m, 1H), 5.31 (d, 1H), 6.21 (d, 1H), 7.24 (dd , '1H), 7.68 (dd,1H), 8.26 (d,1H), 8.53 (s,1H),10.00 (dd,1H) ' Preparation 22 , 3-[4·(Μ-diazepane Small base) pyrimidinyl] carbazole and bite-6-gambling

2.30 (dd,1H), 2.97 - 3.11 (m,2H), 3.15 - 3.24 (m, iH), 3 25' a ) 4-[2-(6-cyanoimidazo[1,2·&lt;ι Acridine-3-yl)pyrimidin-4-yl-azepan-1-carboxylic acid tert-butyl vinegar according to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl) Imidazo[l,2-a]pyridine-6-indolecarbonitrile (Preparation 4b) and 1,4-diazacyclohepta-1-carboxylic acid tert-butyl ester gave a solid (48%). Crude yield can be used without further purification. LRMS (m/z): 420 (M+l)+. H-NMR δ (DMSO-J6): 1.03 (bs, 3H), 1.26 (bs, 4H), 164 201130835 1.56 - 1.98 (m,4H), 3.20 - 3.33 (m,2H) 3 3.81 - 4.05 (m , 2H), 6.71 (d, 1H), 7.70 (dm, · 3.78 (m' 4H)' 8.32 (bs, 1H), 8.51 (s, 1H), 10.42 (bs, 1H)'), 7.91 (d, 1H), b) 3·[4-(1,4-diazepane small group [1,2-fl]pyridine-6-carbonitrile J deep bite 2-base] imidazole and according to preparation 5b In the experimental procedure described, saliva [1,2-&amp;]対_3·yl) is _4_yl)]4_4·(2·(6-cyano-flavored third vinegar (preparation 22a) Obtained solid (^) gas heterocyclic Gengyuan small formic acid LRMS (m/z): 320 (M+l) +. Preparation 23 2-Gas-4-methoxy 啥 琳 琳

CI a) 2,4-dioxaquinazoline quinazoline-2,4(1H,3H)-dione (5.0 g, 30 8 mmol) dissolved in phosphorus oxychloride (50 ml, 546 mmol) The mixture was stirred and heated to 115 C. After 16 hours, the mixture was evaporated, followed by co-evaporation with toluene. The residue was dissolved in ethyl acetate and triethylamine (2 mL). After stirring for 5 minutes, EtOAc (EtOAc m.) LRMS (m/z): 199 (M+l)+. 165 201130835 (: Ζδ(εοα3):7·76(^1Η-·--κ2Η) b) 2-Chloro-4-methoxyquinazoline to the 2,4-dioxin To prepare a solution of sterol (10 ml) in a solution of 5 m H 1 〇 〇 ΐ ΐ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 The solvent was evaporated and the mixture was partitioned. The organic phase was dried (MgS 〇 4) and evaporated to give compound (1,7 g, 96%). Title LRMS (m/z): 195 (M+l)+ 〇!H), 7.88 - 'H-NMR δ (CDC13): 4.23 (s, 3H), 7.57 (ddd 7.84 (m, 2H), 8.17 - 8.11 (m, 1H). Preparation 24 (2-(4- 啥 啥 啥 2 2 _ _ ) 味 味 味 味 并 并 并 并 并 并 并 并 ( ( ( 10 10 10 10 10 10 10

a) 2-(4-methoxylate: base) and 叩 务 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 猜 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照(Preparation 1, W grams, U millimoles) and 2-gas-4-methoxy filaments (Preparation 23b 'G. 32 grams, L6 mmol) afforded white 166 201130835 color solid (74%). LRMS (m/z): 302 (M+l)+. 1H-NMR δ (CDC13): 4.30 (s, 3H), 7.63 _ 7.38 (m 7.86 (dd, 1H), 8.02 (d, 1H), 8.18 (d, 1H), 8.76 (s, 1ΗΓ ^ (s, 1H).,), 10.83 b) (2-(4-hydroxyquinazolin-2-yl)imidazolium pyridinium according to the experimental procedure as described in Preparation 4b, from 3_(4_methyl-month porphyrin· 2_yl)isoxazo[l,2-a]pyridin-6·carbonitrile (preparation, 〇3〇8-base 1.0 mM) gave a brown solid (74%). LRMS (m/z): 286 (M+l)+. Preparation of 25 2-gas-4-methoxy-5-0 than biting-3-yls

a) 5-Bromo-2-oxo-4-methoxypyrimidine A solution of 30% sodium decyl methoxide in methanol (8.0 liters, 42 〇 dropwise added to the cooled (ice bath) 5 bromo-2, 4-dioxane gram, 43.2 mmoles in a solution of sterol (100 ml). The mixture was allowed to warm to room temperature and stirred for 4 hours. The solvent was removed under reduced pressure and partitioned between water and dioxane. The organic layer was washed with EtOAc (EtOAc m. LRMS (m/z): 222/224 (M+l)+. W-NMR δ (CDC13): 4.11 (s, 3H), 8.44 (s, 1H). b) 2-gas-4-methyl group-5-n is squirting nitrogen gas through the 5-bromine methoxycarcinoma contained in the microwave container (preparation 25a, 0.51 g, 2.3 millimoles), pyridyl acid (0.30 grams, 2.5 millimoles) and potassium carbonate (〇93 grams; &quot;6 7 millimoles) in toluene (8.0 ml) and head, · two f base 5 minutes in a mixture of guanamine aQ ml). Next, [1, broad bis(diphenylphosphino)ferrocene] gas (II) and methylene chloride (1:1) complex (68 mg, 0.11 mmol) were added to seal the container. It was subjected to 185 microwave irradiation for 1 minute. The reaction mixture was filtered through a pad of Celite® and washed with ethyl acetate. The combined filtrate and EtOAc were evaporated. ' LRMS (m/z): 222 (M+l) + Preparation 26 3-(4-Hydroxy-5-pyridin-3-ylpyrimidin-2-yl)imidazolium, 2a]pyridine-6-carbonitrile 168 201130835

Yuling 3·Based 2. Base material and pottery according to the experimental procedure as described in Preparation 4a +, 2-mercaptooxy 5 port is compared to indole-3-yl' bite (preparation 25b, 〇226 g , 1 〇 莫 耳 ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) The title compound was obtained as a white solid (yield: EtOAc: EtOAc: EtOAc: 14%) LRMS (m/z): 329 (M+l) + W-NMR δ (CDC13): 4.19 (S, 3H), 6.50 (dd, 1H) 7 44 (ddd, 1H), 7.48 (dd , 1H), 7.85 (dd, 1H), 7.96 (ddd, 1H) 8 62 (s, 1H), 8.67 (dd, 1H), 8.87 (dd, 1H), 10, 56 (dd, 1H). ' b ) 3-(4-pyrimidinyl-bito-3-ylpyrimidinyl)imidazolium (1) Bite-6-A guess according to the experimental procedure as described in Preparation 4b, by 3_(4_甲氡芙$0 ratio咬-3-ylcarcinoma 唆-2-yl) miso and [1,2-α]η ratio bite_6_carbonitrile (Preparation 2) to obtain a brown solid (100%). a LRMS (m/z) : 315 (M+1)+ 〇^-NMR δ (CDC13): 6.86 (d, 1H), 7.91 (d, 1H), 8 〇4 (d 1H), 8.19 - 8.10 (m,1H), 8.81 ( s,1H),9.05 - 8.86 (m 2H)' 169 201130835 9.40 (s,1Η), 10.43 (s,1H). Preparation 27 3-(4-Chloro-6-° ratio bite-3-kee bite- 2-base) miso and [l,2-ii]D than bite

a) 3-(4,6-dimethoxypyrimidin-2-yl)imidazo[1,2·ύτ]pyridine according to the experimental procedure as described in Preparation 4a, from 2-gas-4,6-di The methoxypyrimidine and imidazo[1,2-[alpha]pyridine gave a brown solid (50%). LRMS (m/z): 282 (M+l)+. !H-NMR δ (CDC13): 4.03 (s, 6H), 6.12 (s, 1H), 7.23 (td, 1H), 7.50 (ddd, 1H), 7.78 (dt, 1H), 8.52 (s, 1H) , 9.83 (dt, 1H). b) 2-flavor and [l,2-ii]n than bite-3-base mouth diol according to the experimental procedure as described in Preparation 4b, from 3-(4,6-dimethoxypyrimidine- 2-Based) Imidazo[1,2-α]pyridine (Preparation 27a) gave a brown solid. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <H-NMR δ (DMSO-^6): 5.72 (s, 1H), 7.69 (ddd , 13⁄4) 8.14 - 8.00 (m, 2H), 8.89 (s, 1H), 10.30 (d, 1H). ' c) 3-(4,6-Di-pyrimidin-2-yl)imidazo[1,2-ii]pyridine will 2-merazo[1,2-β]σΗ:^-3-yl pain bite -4,6-diol (Preparation 27b '33 mg, I·45 mmol) Chlorooxidation (7) (28 liters) The solution was heated and stirred to 115. (: After 18 hours, the mixture was evaporated and EtOAcqqqqqqqqqqqqqqq : 7.48 (s, 1H), 7.75 (t, 1H), 8.20 (t 1H), 8.48 (d, 1H), 8.90 (s, 1H), 10.21 (d, 1H) 〇' d) 3-(4- Gas-6-pyridin-3-ylpyrimidin-2-yl) oxazolo[l,2-fl] pyridine biting nitrogen gas through 3-(4,6- contained in Schlenck tube Di-pyrimidinyl-yl) oxazolo[1,2-β]pyridine (preparation 27c, 〇14 g, 0.54 mmol), pyridin-3-ylboronic acid (0.044 g, 0.36 mmol) and 2 IV[ An aqueous solution of cesium carbonate (0.54 mL, 1.08 mmol) was obtained in a mixture of 1,4- dioxane (6 mL) for 5 min. Next, bis(diphenylphosphino)ferrocene]digas was added to seal the container with a mixture of (II) and two gas (1:1) (0.029 g '0.04 mmol). The contents were heated to 90 °C. After 18 hours, the reaction mixture was filtered through Celite® and washed with ethyl acetate. The filtrate was evaporated and purified EtOAc EtOAcjjjjjjj LRMS (m/z): 333 (M+l)+. 171 201130835 Preparation 28 2-Ga-6-[(4-methoxybenzyl)oxy]pyridazine

Sodium hydride (60% mineral oil dispersion, 0.16 g, 4.0 mmol) was added portionwise to stirred 2,6-dichloropyrazine (0.50 g, 3.4 mmol) and (4-methoxy) Phenyl)methanol (0.51 g, 3.7 mmol) in a solution of AW-dimercaptocaramine. The reaction mixture was stirred at ambient temperature overnight, then evaporated in vacuo. The residue was partitioned between EtOAc and EtOAc (EtOAc)EtOAc. The residue was purified by EtOAc EtOAcjjjjjjj LRMS (m/z): 251 (M+l)+. H-NMR δ (CDC13): 3.83 (s, 3H), 5.32 (s, 2H), 6.93 (d, 2H), 7.40 (d, 2H), 8.14 (s, 1H), 8.15 (s, 1H) Preparation 29 3-(6-trans-based 0-indol-2-yl) miso and [1,2-ίϊ] 0 to bite-6-a guess 172 201130835

The dried resealable Schlank tube was charged with 2-chloro-6-(4-methoxyphenoxy)pyrazine (preparation 28, 0.68 g, 2.7 mmol), 11 m. And [l,2-ah-pyridyl-6-indene nitrile (preparation bu 0.59 g, 4.1 mmol), potassium acetate (0.138 g, h41 mmol) and hydrazine, hydrazine, -dimethylacetamide ( 4 ml). The Schlenk tube was subjected to three evacuation cycles with argon backfill followed by hydrazine (triphenylphosphine) palladium (0) (0.34 g, 〇.3 mol). After three additional evacuation cycles with argon backfill, the Schlenk tube was capped and placed in a 1503⁄4 oil bath and the mixture was stirred for 4 hours. The mixture was evaporated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was extracted with aq. EtOAc EtOAc (EtOAc)EtOAc. The organic layer was dried (MgSO.sub.4), evaporated and purified eluting elute ). LRMS (m/z): 238 (M+l)+. Preparation of 30,2H(4-poxybenzaki)_[[15]small phenethylj 啸 -4-4·amine 173 201130835

a) 2· gas-called (15)-1-phenethyl]pyrimidine_4_amine in a sealed tube will be stirred 2,4-dichloropyrimidine (1.27 grams, 8.5 millimoles), 〇S&gt; a mixture of l-phenylethylamine (丨〇 ml, 78 mmol) and diisopropylethylamine (1.6 ml, 8.6 mmol) in the condition #, dimethyl carbamide (12 ml) Heat to 9 〇. Hey. After 16 hours, the mixture was evaporated in vacuo then dissolved in ethyl acetate. The organic layer was washed with EtOAc (EtOAc EtOAc (EtOAc). °/〇) LRMS (m/z): 234 (M+l)+.H-NMR δ (CDC13): 1.59 (d, 3H), 5.38 - 5.75 (m, 1H), 6.08 (d, 1H) ), 7.28 - 7.43 (m, 5H), 7.97 (d, 1H) ' ' b) 2-air nasal (4-methoxybenzyl)-7V_[(ls) small phenylethyl] 唆-4 -Amine sodium hydride (60% mineral oil dispersion, 0.17 g, 4 · 3 mmol) was added in portions to 2-chloro #[(15)-1-phenethyl] shit-4-amine (preparation 3〇a, 〇·95 grams, 4.1 millimoles) in the solution of dimethylformamide (1 ml). The mixture was stirred for 15 minutes, then dimethyl methyl (10) mL, 4.3 mmoles was added and re-enclosed (lower =========================================================================== Dry (MgS 〇 4) and evaporate in vacuo. EtOAc EtOAc (EtOAc) The title compound (0.94 g, 65%) 〇LRMS (m/z): 354 (M+l)+.]H-NMR δ (CDC13): 1.58 (d, 3H), 3.78 (bs, 3H), 4.21 . 4.44 (m, 3H), 6.11 (d, 1H), 6.80 (d, 2H), 6.99 (d, 2H), 7.15 . 7-42 (m, 5H), 7.92 (d, 1H) Preparation 31 M Benzyl-2-gas-iV-methylpyrimidine-4-amine

Methyl-1-phenylguanamine (0. 32 ml, 25 mmol and diisopropylethylamine (〇.58 ml '3.3亳莫耳) was added sequentially to ^1 gas (0.50 g, 3.4 m) In the solution of the oxime in the succinylamine (5 liters) solution, the mixture was refluxed for 3 hours in a sealed tube. The mixture was evaporated, the residue was dissolved in ethyl acetate, washed with water and dried. The title compound ( 〇 51 g, 86%) was obtained as an oil. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 234 (M+l)+. ^H-NMR δ (CDC13): 3.08 (bs, 3H), 4.79 (bs, 2H), 6.35 175 201130835 (d, 1H), 7.14 - 7.41 (m, 5H), 8.04 (d, 1H) Preparation 32 (5^-6-gas-N-(l-phenethyl)0-e-qin-2-amine

Obtained in white according to the experimental procedure as described in WO200399796 from 2,6-dichloropyrazine (1.92 g, 12.9 mmol) and (5&gt; 1-phenylethylamine (1.72 g, 14.2 mmol) Solid (37%) LRMS (m/z): 234 (M+l) +. NMR δ (CDC13): 1.58 (d, 3H), 4.86 (bs, 1H), 5.08 (bs, 1H), 7.24 - 7.32 (m, 5H), 7.60 (s, 1H), 7.79 (s, 1H) Preparation 33 1-(ethylsulfonyl)-7V,4-dimethylpiperidin-3-amine

a) (1-Benzyl-4-methylpiperidin-3-yl)methylcarbamic acid tert-butyl ester 176 201130835 A sequential triethylamine (1.72 ml, 12 3 mmol) and two Dish Acid II + 3 Ding from the purpose (2.7G gram ' 12.4 亳 Mo Er) added to the riding cis 1 benzyl group - dioxin based bite _3_ amine (such as w〇2〇〇56〇972 Prepare a solution of '2.7 G grams ' 12.4 mmoles) in dichloromethane ((9) mL). At (iv) temperature _ mixture overnight. The title compound (3.40 g, · 〇) was obtained as a solid, using a saturated aqueous solution of sodium bicarbonate, water, and ss. 319 (M+l)+. NMR 6 (CDC13): 1.00 (d, 3HX 1.51 (s, 9H), 1.64 (bs, 1H), L98 (bs, 2H), 2.24 (bs, 2H), 2 49 (10), ih), 2 77 (10) 2H), 3.16 (s, 3H), 3.50 (s, 2H), 7.23 - 7.45 (m, 5H) b) methyl (4-methylbend-3-yl)amine Tert-butyl carboxylic acid, cadmium/charcoal (1%, 0.30 g) was added to; _benzoyl-based ice methyl-derived-3-yl) decyl-based carboxylic acid, third butyl (preparation ❿, 3 The mixture was stirred for 20 hours under a hydrogen atmosphere in a solution of 4 gm, 10.7 mmol of methanol (7 gm). The title compound (2.38 g, 97%) was obtained. LRMS (m/z): 229 (M+l)+. ^H-NMR δ (CDC13): 0.94 (d, 3H), L39 (s, 9H), 1.58 . 1.68 (m, 1H), 2.11 - 2.20 (m, 2H), 2.68 (bs, 1H) 2.73 - 2 (m, 2H), 2.83 (s, 3H), 2.99 (bs, 2H) ' ' \ · e MM methyl _·3·yl] methyl methacrylate tert-butyl ester ^ will continue to bismuth chloride (0.86 A milliliter, 9 a millimole of dichloromethane (3 177 201130835 ml) solution was added dropwise to the stirred and cooled (ice bath) methyl (4 hydrazin-3-yl) amino citrate tributyl hydrazine (Preparation, 89 g, 8.3 mmol) in a solution of methylene chloride (60 ml) and triethylamine (1) 7 ml '9.1 mmol. The mixture was warmed and mixed overnight. The title compound (2.20 g, 83%) was obtained as a solid. LRMS (m/z): 321 (M.sub.2). M+l)+. ^-NMR δ (CDC13): 1.00 (d, 3H), 1.38 (t, 3H), 1.46 (s, 9H), 1.65. 1.76 (m, 2H), 2.04-2.14 (m, 1H), 2.96 (d, 2H), 2.98 (s, 3H), 3.05-3.18 3.33 (bs, lH), 3.51 (bs, lH), 3.64 (bs, 1H) d) 1-(ethenesulfonyl) -7V,4_Dimethylpiperidine j amine A solution of trifluoroacetic acid (12.25 ml, 159 mmol) in dichloromethane (1 mL) was added to stirred and cooled (ice bath) M_Methyl bucky-3-yl (methyl) carbamic acid tributyl sulfonate (prepared to say 3 gram, 9.4 mmol) in dichlorohydrazine (22 ml). Allow the mixture to warm to room temperature and mix overnight. The solvent was evaporated, and the residue was basified with 2M aqueous sodium hydroxide, and then the organic solvent was removed under reduced pressure to afford the title product as oil. Gram, 97%). . (2. 〇6 LRMS (m/z): 221 (M+l)+. b-NMR δ (CDC13): 1.24 (d, 3H), 1.63 (t 3 1-91 (m, 2H), 2.25 - 2.36 (m, 1H), 2.81 (bs, lHU.9〇178 201130835 3.06 (bs, 1H), 3.21 - 3.37 (m, 1H), 3.42 - 3.51 (m, 1H), 3.68 (bs, 2H), 3.91 (s, 3H) Preparation 34 cis-3-(3-Amino-4-methyl-p--1-yl)-3-oxo-propanoid

a) (4-methylpyridin-3-yl)carbamic acid tert-butyl ester bis(trimethylsulfonylalkyl)amino sodium (1 Μ tetrahydrofuran solution, 32.0 mL, 32.0 mmol) was added dropwise A solution of 4-methyl 0-pyridin-3-amine (1.72 g, 15.9 mmol) in tetrahydrofuran (30 mL) was cooled (br.). The mixture was allowed to warm to ambient temperature and stirred for 5 minutes. The mixture was again cooled to 0 ° C and a solution of di-tert-butyl dicarbonate (3.09 g, 14.2 mmol) in tetrahydrofuran was added. The mixture was allowed to warm to ambient temperature and stirred for 18 hours. The pH of the mixture was adjusted to 5-6 using a 0.1 Torr aqueous solution of hydrochloric acid. The title compound (2.16 g, 70%) eluted LRMS (m/z): 209 (M+l)+. ^-NMR δ (CDC13): 1.43 (s, 9H), 2.27 (s, 3H), 6.25 (bs, 1H), 7.10 (d, 1H), 8.23 (d, 1H), 8.86 (s, 1H). b) cis-(4-methylpiperidin-3-yl)carbamic acid tert-butyl ester 179 201130835 to (4-decylpyridin-3-yl)amino decanoic acid tert-butyl ester (Preparation 34a, 1.9 Add 5% bond/carbon (1.0 g) to a solution of gram (9.2 ml) of sterol (15 ml). The mixture was hydrogenated at 50 ° C (60 sec/square leaf pressure) for 48 hours. The catalyst was filtered through Celite® and the filter cake was washed with methanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was purified by flash chromatography (98··············· The title compound (0.60 g, 31%). LRMS (m/z): 215 (M+l)+. ^NMR δ (CDC13): 0.91 (d, 3H), 1.28 (d, 2H), 1.45 (s, 9H), 1.71 (bs, 5H), 2.59 (t, 1H), 2.72 (d, 1H), 2.96 (d, 2H), 3.68 (d, 1H), 5.30 (d, 1H). ' c ) cis-indole 1-(cyanoethenyl)-4-methylpiperidin-3-yl]carbamic acid tert-butyl ester, followed by triethylamine (0.26 ml '1.8 mmol) and 3_[(2,5·one-side oxy 11-pyrrolidin-1-yl)oxy]-3-oxo-propanenitrile (prepared as described in BE 875054 (A1), 0.364 g, 2. 〇 mmol The ear was added to a stirred solution of cis-4-mercaptopiperidin-3-ylamino decanoic acid tert-butyl ester (preparation 34b, 0.36 g, 1.7 mmol) in di-methane (6 mL). The mixture was stirred at ambient temperature for 24 hours and then evaporated. Water was added and the mixture was taken freshly with dichloropurine. The organic layer was dried <RTI ID=0.0>(M </RTI> <RTI ID=0.0></RTI> </RTI> <RTI ID=0.0></RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; LRMS (m/z): 282 (M+l) + ^-NMR δ (CDC13): 0.99 (d, 3H), 1.29 (qd, 1H), i 46 (s 180 201130835

In the water. Then dissolved in saturated sodium bicarbonate;

~1 milk 1r炕i / ml) solution. The mixture was then evaporated and the aqueous solution was dissolved to bring the mixture to a neutral pH and extracted with di-methane. The organic layer was dried (M.sub.4) and evaporated. EtOAcjjjjj Gram, 72%). LRMS (m/z): 182 (M+l)+. W-NMR δ (CDC13): 0.96 (d, 3H), 1.58 - 1.48 (m, 1H), 1.90 _ 1.76 (m, 2H), 2.73 (ddd, 1H), 3.03 - 2.88 (m, 1H), 3.32 -3.24 (m, 1H), 3.64 (d, 2H), 3.88 - 3.76 (m, 1H), 4.47 - 4.22 (m, 1H). Preparation 35 cis-1-(ethylsulfonyl)-4-methylpiperidineamine

a) cis-[1-(ethylsulfonyl)-4-methylpiperidine]aminoguanidine tert-butyl ester 181 201130835, diethylamine (〇.33 ml '2.3 mmol) and B. Helium (0. Π ml, L7 mmol) was added to the cooled (ice bath) cis-(4-methyl-bottom-3-yl)-amino-butadiene acetonitrile (preparation g g, 1.2 Milligram) in a two-gas ablation (3 ml) solution. The mixture was allowed to warm to ambient temperature for -18 hours. Water was added and the organic layer was washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by flash chromatography eluting elut elut elut elut elut LRMS (m/z): 307 (M+l)+. H-NMR δ (CDC13): 0.96 (d, 3H), 1.44 (s, 12H), 1.62 (s, 1H), 1.80 - 1.66 (m, 1H), 2.74 (t, 1H), 2.93 (dt, 3H) ), 3.49 (d, 1H), 3.80 (dd, 3H), 4.95 (d, 1H). 'b) cis-1-(ethylsulfonyl)-4-methylpiperidin-3-amine according to the experimental procedure as described in Preparation 34d, to give Shun [J] Piperidin-3-yl]amino decanoic acid tert-butyl ester (preparation 35a, 03 〇 5 g '1.0 mmol). Evaporate the crude mixture, add water, then basify the mixture with saturated aqueous sodium bicarbonate solution. The title compound (0.145 g, 70%) was obtained as an oil. LRMS (m/z): 207 ( M+l)+. iH-NMR δ (CDC13): 1.01 (d,3H), 1.45 _ 1.22 (m,3H) 1.60 (d,4H), 2.85 - 2.73 (m, 1H), 3.13 - 2.85 (m , 3H), 3 86 _ 3.47 (m, 2H). Preparation 36 182 201130835 Iodinated 1-((25,45)-2-cyano-4-fluoropyrrolidine-1-carbonyl)-3-indenyl- 1H-imidazole-3-indole

Two I·two

FF Iodine (0.075 mL, 1.2 mmol) was added to the stirred (2乂4S&gt; 4-fluoro-1-(1H-imidazol-1-carbonyl)pyrrolidin-2-indenecarbonitrile (0.29 mmol) The title compound (99%) was obtained as a solid, EtOAc (EtOAc) It can be used without further purification. LRMS (m/z): 223 (M-1) · Preparation 37 Iodinated 1-((cyanomethyl)(methyl)aminecarbenyl)-3-A base_1H-imidazole-3-indole

a) 7V-(cyanomethyl)methyl-1 and -imidazole-1-cartoamine According to the experimental procedure described in US2005256310 (A1), 2-(methylamino)acetonitrile (1 g, 14.3 m) Mohr) reacted with 1, hydrazine-carbonyldiimidazole (2.5 183 201130835 g, 15.4 mmol). The crude product was purified by flash chromatography eluting elut elut elut elut elut LRMS (m/z): 165 (M+l)+. ^-NMR δ (CDC13): 3.28 (s, 3H), 4.37 (s, 2H), 7.15 (s, 1H), 7.30 (bs, 1H), 7.97 (s, 1H) b) iodide 1-(( Cyanomethyl)(methyl)aminemethanyl)-3-methyl-i ugly-imidazole-3-indole according to the experimental procedure as described in Preparation 36, from Λ-(cyanoguanidino)- #-Methyl·///-Imidazolium-1-decylamine (Preparation 37a, 0.24 g, 1.46 mmol), and iododecane (0.36 mL, 5.9 mmol) afforded oil (45%). The isolated crude product was used without further purification. LRMS (m/z): 179 (M-Ι)·. ^-NMR δ (DMSO-J6): 3.34 (s, 3H), 3.91 (s, 2H), 4.64 (s, 3H), 7.06 (bs, 1H), 7.58 (bs, 1H), 8.09 (s, 1H) Preparation of 38 2-decyloxy-4·(4,4,5,5-tetradecyl-1,3,2-dioxanthene 4_2·yl) 0 bite

Nitrogen gas was bubbled through the 4-iodo-2-decyloxypyridine (0.099 g, 0.42 mmol), bis(pinacol) diboron (0.12 184 201130835 g, 0.47 mmol) contained in the microwave vessel. And a mixture of potassium acetate (0.13 g, 1.31 mmol) in dimercaptocaramine (ml) for 5 minutes. Next, a composite of [U'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and dioxane methane (1:1) (0.017 g, 0.02 mmol) was added to seal the container. And subjected to microwave irradiation at 80 ° C for 4 hours. The reaction mixture was diluted with ethyl acetate and dried over Celite. The filtrate was washed with aq. EtOAc EtOAc EtOAc (EtOAc m. z): 236 (M+l)+. Preparation 39 1 is better than 嗤-3-carboxylic acid

A 2 oz. aqueous solution of sodium hydroxide (18 ml, 3 6 mmol) was added to a solution of pyrazole _4_ decanoate (0.2 g, 1.55 m. The reaction mixture was stirred at room temperature overnight and stirred for additional 2 hours under ribs. Ethanol was evaporated and the mixture was neutralized to give crystals. * LRMS (m/z): 113 (M+l) + 〇 Preparation 40 185 201130835 〇Ε)-4-Aminotricyclo[3.3.1.13,7]nonanol

To 4-{[(1 phantom-1_phenethyl)amino}adamantan-1-ol (0.400 g, 1.47 mmol; prepared as described in ~10 (2006), 47, 8063) 10% palladium/charcoal (33 g) and ammonium formate (0.430 g, 6.82 mmol) were added to the ethanol (58 ml) solution. The reaction mixture was stirred at 85 ° C for 1 hour, followed by Celite®. Filtration and evaporation of the EtOAc EtOAc EtOAc (EtOAc) m,5H), 1.7-1.83 (m,6H),1.9 (m,3H), 1.94 (m,1H),2.09 (m,1H), 3.01 (bs, 1H) ° Preparation 41 (Z)_4_amine Tricyclic [3.3.1.13'7] indole-1-ol

The title was obtained according to the experimental procedure as described in Preparation 40, from the corresponding Z isomer (0.102 g, 0.38 mmol; prepared as described in nar/ze 〇 «· Z(10) 2006, 47, 186 201130835 8063) Compound (99%). The crude product was used in the next step without further purification. § (CDci3): L5M.4(m, 2H), )h 6H), L91 8 (m, 4H), 2·09-2·00 !Η), 2.87 (bs, 1H). Preparation 42 3_(4'5--gas 'bit-2-yl)-6_ astringent wow and [12 but pyridine

a) 6_fluoroimidazo[1,2-φ-pyridyl_3_indenecarbonitrile 1 brompyrrolidine_2,5_dioxin (15 8 g, 89 2 mmol) is added to the branch (Ice bath) and stirred __ methoxy propylene guess (749 ' 89.2 millimoles) of the second. In the solution of cacao/water (3: Bu 600 ml). The solution was aged for 3 () minutes at G ° C, followed by the addition of 5 oxime &gt; amine (5.0 g, 44.6 mmol). The mixture was allowed to warm to ambient temperature over 2 hours' then heated to 6 Torr and stirred at 6 (Tt under 16 λ!). The organic shaft was removed under reduced pressure and the residue was partitioned between ethyl acetate and sodium carbonate. The crude product was purified by flash chromatography (15·············· LRMS (m/z): 162 (M+l)+ 〇187 201130835 m) δ (face (10)): 7·71 (ddd, 1H), 7.9 (four), &49 (s,1H),8·98 ( Bs, 1H). b) 6-fluoroimidazo[1,2 &lt;|] pyridine carbonyl hydrazide phthalamide to: fluoro-salt and tl, 2_a]n than carbonitrile (5 6 grams, Μ Γ Γ 仏) Me 〇H (8 〇 ml) solution was added to add methanol to the main t' 3.4 mmol. The mixture was stirred at ambient temperature for 17 hours, and ammonium sulfate (2.05 g, 38 3 mmol) was added and the mixture was refluxed for 4 hours. The solvent was removed under reduced pressure and the obtained solid was washed with ethyl acetate (8x30m). The title compound (9) was obtained as a brown solid. /. And it was used in the next step without further purification. LRMS (m/z): 179 (M+l)+. δ H-NMR δ (DMSO-J6): 7.70 (dd, 1H), 7.89 (dd, 1H), 8.35 (s, 1H), 8.85 (brs, 1H). c) 5-gas-2-(6-fluoro-scented [l,2_d]T» than bite_3_base) shouted bite _4_alcohol to nano (0.9 g '39.1 mmol) of methanol (5 〇ml)) solution of 6-fluoroimidazo[l,2-a]pyridine-3-carbonylindoleamine (3.5 g ' 19.6 mmol, preparation 42b) and 2-ox-3-oxooxy Ethyl propionate (5.8 g '38.5 mmol). The mixture was refluxed for 18 hours with vigorous stirring. The reaction mixture was allowed to cool to ambient temperature and filtered. The obtained solid was washed with EtOAc EtOAc (EtOAc) LRMS (m/z): 265 (M+l)+. 'H-NMR δ (DMSO-J6): 7.43 (dd, 1H), 7.73 (dd, 1H), 7.95 (s, 1H), 8.26 (s, 1H), 10.18 (dd, 1H). 201130835 d) 3_(4,5-dioxapyrimidine_2_yl)&amp;Sprayed 5-chloro-o-degas in the subsidiary; ^ and [1,2 rushed than the chlorpyrifos I alcohol (2.6 g, Μ Μ Mozol and [丨, 2·# than bite _3_ base) 醯 (26 ml) solution for 3 hours. The three gas (four) will be tested with 8 N hydroxide and slowly added to the water with acetic acid, and the right side of her ia B A, Shi rot, 3 extraction. The organic solvent was removed by washing with water and brine, and the title LMS (m/z)·· 284 (M+l)+ was obtained. !Η), 7.75 (dd, 1H), 8.66 丨H-NMR δ (C0C13): 7.34 (ddd, (s, 1H), 8.70 (s, 1H), 9.75 (dd, 1H). Preparation 43 5· -2_(6-fluoroimidazo[1,2-fl]pyridylpyrimidine-4-amine

a) (3Ι?)·3·{[5·气·2. (4) Sodium and (10) bite each base (four) bite · 4-yl] amine group} brigade bite 1-carboxylic acid third vinegar to make 3-( 4,5-one azide bite_2_yl)_6• odor oxazole [^2 ^^ (0 52 g, I.84 mmol 'preparation 42d) and (λ)_3_amine base bite small formic acid Tributyl ester (1.12 g, 5 59 mmol) in ethanol (4 mL) 189 201130835 LRMS (m/z): 447 (M+l)+. b) 5-Gas-2-(6-fluoroimidazo[i,p-β]pyridin-3-yl]pyrimidine_4_amine = according to the experimental procedure described in Preparation 5b, postal 3|chlorine 2 (6•Fluorinated [1,2 rushed to the -3-yl group) ♦ _4_yl]amino-based hazelnic acid tributyl acrylate (preparation 43a) to obtain a solid (4%). LRMS (m/z): 347 (M+l) + H-NMR δ (CDC13): 1.64 (bs, 1 Η), 1.80 (dd, 2 H), 1.92 -2.00 (m, 1 H), 2.81 - 2.92 (m, 3 H), 3.24 (dd, 1 H), 4.26 -4.35 (m, 2 H), 5.92 (bs, 1 H), 7.23 (dd, 1 H), 7.67 (dd, 1 H) , 8.22 (s, 1 H), 8.51 (s, 1H), 9.87 (dd, lH). Preparation 44 3-(4-Azuldin-2-yl)-6-fluoroimidazole and pyridine

On a CI, 2·(6-fluoroimidazo[12-glycol-3-yl) sulphonate (〇.95 g' (η mmol, preparation 8) and gas oxidized scale (8 31) The mixture of ML, 9G.78 millimolar was heated to a scratch. Under reduced pressure 19〇201130835 After removing excess phosphorus oxide, the residue was dissolved in ethyl acetate and sequentially with water, 4% aqueous argon carbonate solution and The organic phase was dried with EtOAc (EtOAc m.) !H-NMR δ (CDC13): 7.16 (d, 1H), 7.35 (ddd, 1H), 7.79 (dd, 1H), 8.66 (d, 1H), 8.69 (s, 1H), 9.89 (dd, 1H) Preparation 45 (5)-1_(2-(6-1 mercapto(10) but pyridine·3yl) hydrazide _4·yl) hydralidine-2-carboxylic acid

a) (5)_1_(2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidin-4-yl)pyrrolidin-2-carboxylic acid methyl ester 3_(4-apyrimidine _2-fluoroimidazole &amp; tl, 2_a] pyridine (14 〇 mg, 〇. 56 mmol, preparation 44), 〇S&gt;n ratio 咯 曱-2-methoxyglycolate hydrochloride (140 mg 〇 · 85 mM) and a mixture of triethylamine (200 μl, 1.43 mil:): methanol (1 mL) heated to reflux overnight. The gas was burned between the three gas and the water. The organic layer H 4% aqueous solution of hydrogencarbonate and the brine were separated, dried over sodium sulfate and the solvent was removed under reduced pressure. by flash chromatography (2 gas yam 191 201130835 to The title compound (16 Gt, 83%) was purified by methylene chloride / methanol (methanol): </ RTI> </ RTI> </ RTI> NMR (m/z): 341 (M+). iH-NMR5 (CDCl3): 2.14 (td, 3H) 2 37 ( Dd 2_ 3.60 3.62-3.71 3.76 (s, 3H), 4:81; S; 1H), 6.26 (bs, 1H), 7.22 (dd, 1H), 7.66 (machine 8.50 (s, 1H), 9.90 (bs, 1H) (,), b) (5)-1-(2-(6-fluoro-salt, 2 bis-pyridylpyrrolidine-2-carboxylic acid (5)-1-(2-(6) - Fluorine π sitting and [to ♦ bit _3_ base) mouth bite冰 〇 唆, 唆-2-carboxylate methyl ester (122 mg, 0.36 mmol, preparation 45a) with aqueous sodium hydroxide (2 N '536 μl, 1·〇7 mmol) in decyl alcohol ( The mixture in 1 mL) was heated to 5 ° C until the reaction was completed. The solvent was evaporated under reduced pressure and the residue was suspended in water, neutralized with 2N aqueous hydrochloric acid, filtered and purified by reverse phase chromatography (from Water </ RTI> C-18 SiO2, water/1:1 acetonitrile decyl alcohol as a dissolving agent [0% to 100% by 0.1% v/v citric acid buffer) 98 mg, 84%) LRMS (m/z): 327 (M+).--NMR δ (CDC13): 2.14 (ddd, 1H), 2.25 - 2.57 (m, 3H), 3,45'3·63 ^ 1H), 3.69 (t, 1H), 4.67 (dd, 1H), 6.28 (d, 1H), 7·18 (ddd, 1H), 8.01 (dd, 1H), 8.24 (d, 1H), 8.74 ( s,1H), !〇.〇2 (dd, 1H) 〇. Preparation 46 (β)-1-(2-(6-fluoroimidazo[wa]pyridine·3_yl)pyrimidin-4-yl)pyrrole 192 201130835 Pyridine-2-carboxylic acid

〇a) (and)-1-(2-(6-fluoro-salt and a) bite each base) _4_ base) ° 洛 bite-2-carboxylic acid methyl vinegar will 3 (4· 气 咬 咬 base ) 6-fluoro-flavor α sitting and [1, 2-chaotic] ° bite (140 mg '〇.56 mmol, preparation 44), (8) pyrrolidine-2-carboxylic acid methyl ester hydrochloride (14 〇) A mixture of milligrams '0.85 millimolars' and triethylamine (200 microliters, 1.43 millimoles; in f alcohol (Η)) was heated to reflux overnight. The solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and water. The knife was separated from organic hydrazine, 4% aqueous bicarbonate solution and the salt dried over sodium sulfate and solvent was evaporated under reduced pressure. The title compound (42 mg, 22%) was purified by flash chromatography (dichloromethane to hexanes: 92:8). Solid LRMS (m/z): 341 (M+). iH-NMR δ (CDC13): 2.15 (m,3H) 3.42 _ 3.59 (m,1H), 3.64 - 3.74 (m,lm · — 2.47 (m ,1H), (bs,1H), 6.27 (bs, 1H), 7.24 (t,1H),7·71' μ% (S' 3H)' 4·80 1H), 8.50 (s,1H), 9.90 (bs, 1H). (d,1H), 8,31 (d, b) (=-(iv) primary saliva and U,2, pidyrrolidine-2-carboxylic acid 193 201130835 according to the experimental procedure as described in Preparation 45b , from - fluoromi 0 sitting and [l, 2_a] D than biting _3_ base) bite _4_ base (four) Luo. Ding _2_ citrate 曱酉 (1 〇 mg '0.03 mmol, prepared 46a) Obtained as a white solid (22%). LRMS (m/z): 327 (M+).--NMR δ (CDC13): 2.15 (d, 2H), 2.25 - 2.55 (m, 4H), 3.46 - 3.62 ( m, 2H), 3.63 - 3.77 (m, 1H), 4.67 (dd, 2H), 6.28 (d, 1H), 7.18 (ddd, 1H), 8.00 (dd, 1H), 8.25 (d, 1H), 8.74 (s, 1H), 10.03 (dd, 1H) ° ' Preparation 47 2-((1/·,4ι*Η-Aminocyclohexyl)acetonitrile

a) (lr, 4r)-4-(cyanomethyl)cyclohexylaminoformamidine tert-butyl ester ((lr,4r)-4-(t-butoxycarbonylamino)cyclohexyl) at 55C Methyl methanesulfonate (70 mg, 0.18 mmol, prepared as described in WO2005/87761) and sodium cyanide (3 mg, 〇61 mmol) in Dms(1 mL) The mixture was heated overnight. The reaction mixture was diluted with EtOAc EtOAc (EtOAc)EtOAc. The crude residue (50 mg, 1 〇〇〇 / 〇) was used in the next synthetic step without further purification. 194 201130835 iH-NMR δ (CDC13): 0·99 _ 1.30 (m, 4H), i 44 (s, 9H), 1.55 - 1.71 (m, 1H), 1.91 (d, 2H), 2.06 (d, 2H) ), 2.26 (d, 2H), 3.31 - 3.43 (m, 1H), 4.39 (bs, 1H). 'b) 2-((lMr)_4-Aminocyclohexyl)acetonitrile hydrazine salt (lr, 4r; HK cyanomethyl) cyclohexylamine decanoic acid tert-butyl ester (Preparation 47a '0.348 g, 1.46 Millol) was added to 4 μ of hydrochloric acid. The resulting solution was dissolved overnight (3.65 ml) and at room temperature. The solvent was evaporated in vacuo and the residue was taken diethyl ether. The title compound was obtained as a white solid ( 〇 226 cc, </ RTI> </ RTI> LRMS (m/z): 139 (M+H) + 〇 A , 89%).屯-NMR δ _SCW6): U4 _, 2H), 丨 1.60 (m, 1H), 1.83 (d, 2H), 1.99 (d, 2H), 2.5 〇 (d ^ : (m, 1H), 8.08 (br s, 2H), α, 2H), 2.94 Preparation 48 (and)-2-(6-fluoroimidazo[i,2_a] bit _3·yl)·5_ pyridine-3-yl)pyrimidine-4 -amine methyl-Ν-(η ratio slightly

a) (1〇·3·(2·(6-fluoro-salt and [12_啦 bit_3 · -4-ylamino)) 洛洛 bite-1-carboxylic acid: vinegar vinegar shouting according to As described in Preparation 5a, the experimental procedure consists of &gt; [1, 2♦ than biting-3-yl)-5-methylpyrimidine _4 'smell wow, and 1.43 millimoles 195 201130835 ear 'preparation 19b And (i?)-3-aminopyrrolidine·ι_carboxylic acid tert-butyl ester (533 mg ' 2.86 mmol, prepared as described in US 2009/2215665) to give an oil (263 mg, 45%) . LRMS (m/z): 413 (M+l)+. H-NMR δ (CDC13): 1.42 - 1.53 (m, 2H), 1.60 (Sj 9H) 2.37 (bs, 1H), 2.64 (s, 3H), 3.57 (bs, 2H), 3.85 (bs, 1H) , 4 ^ (s, 1H), 4.81 (bs, 1H), 7.22 (dd, 1H), 7.68 (dd, 1H), 8.10 (sb) (i?)-2-(6-fluoroisoxazole[l , 2-a]pyridin-3-yl)-5-methyl#(bite-3-yl)pyrimidin-4-amine according to the experimental procedure as described in Preparation 5b, from 0)_3_(2_(6_ Flumiimidate=and [l,2-a]acridinyl)_5_mercaptopyrimidinyl-4-ylamino)πpyridine octadecyl acid tert-butyl ester (263 mg, 0.64 mmol, preparation 48a) And triacetic acid (245 μl, 3.18 mmol) gave a white solid (156^78%), N, LRMS (m/z): 313 (M+l)+. ]Η-ΝΜΚ δ (CDCls): 1.74 - 1.87 (m, 2H), 2.08 (s 237 (ddd, 1H), 2.92 - 3.10 (m, 2H)&gt; 3.16 (dt, 1H), 3.36 (dd), 4.72 (dt,1H), 4.82 (bs,1H), 7.21 (ddd,1H), 7.67 (dd' 1Ή), 8.06 (s,坩), 8.51 (s,1H),10.01 (dd,1H). Preparation 49 196 201130835

Nh2

, N〇2

Ketone a) is called fluimibe, 2 is based on the base of the spider 4 is called 6 in the sealed tube will be [U-al amine [preparation 42b, l. 〇 3 grams, 5 75 millimoles, boring · Imino hydrazine nitroacetic acid B-cage, ear ml '34.4 mmoles) in ethanol (15 ml) = mixed =, (4.8 = post-dimensional hour. Evaporate the solvent and divide the residue into two:: ==和^_Water layer several times. Dry filtered over magnesium sulfate and evaporate the solvent to give a semi-solid residue, 3 and a solution of the rabbit aqueous solution, enchanting solid, (d), washing with water and U to give the title compound as a solid (123 g, 78%) LRMS (m/z): 274 (Ml) + ^H-NMR δ (DMSO-^): 7.48 - 7.61 (m, 2H), 7.74-7.88 b) 3-(4 - gas · 5 - county shot 2_ base) heart (four) saliva and sputum to occlude gas oxidative barrier (10 ml) added to 2_(6_ odor 嗤 and (10) ^ pyridyl-3-yl)-5- In the case of Zhajiyi-4 (called steel (prepared gamma, iu gram, * 〇7 mM), the resulting suspension of the cake was maintained for 2 hours after the sealed towel was heated to 9 (rc). Evaporation _, dissolved in two gas The simmered towel was then neutralized to pH 7 by the addition of an aqueous solution of sodium bicarbonate. The organic layer was separated and used with a gas 197 20113 0835 The number of layers of the water to be extracted: owed. The title compound was obtained as a yellow solid (〇81 g, 68%) °LRMS (m/z): 294 (M+l)+ H-NMR δ (CDC13): 7.47 (ddd, 1H), 7.84 (ddd, 1H) 8.84 (s,1H), 9.35 (s,1H), 9.83 (ddd,1H). c) 2-(6-fluoroimidazo[1,2π]pyridine·3_yl)_^((5-fluoropyridine·2yl)methyl)-5-terminal shout-4-amine will be divalent Propylethylamine (742 μl, 4.26 mmol) and (5-fluoropyridin-2-yl)guanamine dihydrochloride (275 mg, 1.38 mmol) were added to the mixture. (4-Ga-5-nitropyrimidin-2-yl)-6-fluoroimidazo[i,2_a]e ratio (preparation 49b, 250 mg, 0.85 mmol) of tetrahydropyrene (8 The mixture was stirred in EtOAc (3 mL, EtOAc) 384 (M+l)+. iH-NMR δ (DMSO-wood): 5.01 (d, 2Η), 7.55 _ 7.74 (m 3H), 7.87 (dd, 1H), 8.54 (d, 1H), 8.56 (s , 1H), 9.25 (s im 9.47 (dd, 1H), 9. 73 (t, 1H). 'Into the preparation of 50 (2-(6-fluoroimidazo[i,2-a]" than pyridine-3-yl)-5- surely carbyl)-5,6,7,8-tetrahydroindole Guanamine 198 201130835

According to the experimental procedure as described in Preparation 49c, from 3-(4-a-5-nitropyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridine (Preparation 49b) and 5, 6,7,8-Tetrahydroquinolin-5-amine gave a yellow solid (51%). LRMS (m/z): 406 (M+l)+. Preparation of 51 (i?)-2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-7V-(3-methylbutan-2-yl)-5-nitro mouth bite _4-amine

According to the experimental procedure as described in Preparation 49c, from 3-(4-a-5-nitropyrimidin-2-yl)-6-fluoroimidazo[1,2-a]-pyrididine (Preparation 49b) and Magic-3-mercapto-2-amine gave a yellow solid (126 mg, 85%). </RTI> </RTI> </RTI> <RTIgt; </RTI> <RTIgt; 2-a]pyridine-3-yl)-7V-(l-methoxypropan-2-yl)-5-fluorenylbite-4-amine 199 201130835

According to the experimental procedure as described in Preparation 49c, 3-(4-Ga-5-nitropyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridine (120 mg, 0.41 mmol) For the ears, see Preparation 49b) and the commercially available mercaptobutan-2-amine (47 mg, 0.53 mmol) afforded a yellow solid (115 mg, 81%). LRMS (m/z): 347 (M+l) + Preparation 53 2-((1 r,4/*)-4-(2-(6-fluoroimidazo[1,2-a]-p-pyridine. -yl)-5-nitropyrimidin-4-ylamino)cyclohexyl)acetonitrile

According to the experimental procedure as described in Preparation 49c, from 3-(4-chloro-5-nitropyrimidin-2-yl)-6-fluoroimidazo[l,2-a]pyridine (Preparation 49b) and 2- ((lr, 4r)-4-Aminocyclohexyl)acetonitrile hydrochloride (Preparation 47b) gave a yellow solid (81%). LRMS (m/z): 396 (M+l)+. 200 201130835 ]H-NMR δ (CDC13): 1.27 (d, 1H), 1.37 - 1.61 (m, 4H), 1.85 (m, 1H), 2.10 (d, 2H), 2.39 (m, 3H), 4.25 ( m, 1H), 7.39 (br t, 1H), 7.78 (dd, 1H), 8.41 (d, 1H), 8.72 (s, 1H), 9.27 (s, 1H), 9.88 (m, 1H). Preparation 54 (l/*, 4r)_4-(2-(6-fluoroimidazo[l,2-a] °pyridin-3-yl)-5-nitropyrimidin-4-ylamino)-1 -methylcyclohexanol

According to the experimental procedure as described in Preparation 49c, from 3-(4-chloro-5-nitropyrimidin-2-yl)-6-fluoroimidazo[l,2-a]acridine (110 mg, 0.37 m Mole, see Preparation 49b) and (lr, 4r)-4-amino-1-methylcyclohexanol (prepared as described in WO2006/76595) afforded a yellow solid (55%). LRMS (m/z): 387 (M+l)+. ^-NMR δ (DMSO-for): 1.26 (bs, 4H), 1.64 (bs, 3H), 1.78 (m, 1H), 2.01 (m, 2H), 4.31 (m, 1H), 4.48 (s, 1H) ), 7.75 (m, 1H), 7.97 (m, 1H), 8.67 (s, 2H), 9.24 (s, 1H), 9.82 (m, 1H). Preparation 55 2-(6-Fluoroimidazo[l,2-a]pyridin-3-yl)-7V-(l-(5-fluoropyridin-2-yl)-2-methoxyethyl)-5-yl Shouting bite 4-amine 201 201130835

According to the experimental procedure as described in Preparation 49c, from 3_(4_气_5_ nitro-nose-2-yl)_6_fluoromime-[1,2 external ratio bite (12〇 mg, 0.41 mmol) For the ears, see Preparation 49b) and 1-(5-fluoropyridin-2-yl)-2-methoxyethylamine (76 mg, EtOAc: 45 mmol) afforded a yellow solid (85%). LRMS (m/z): 428 (M+l)+. H-NMR δ (DMSO-i/6): 3.34 (s, 3 Η), 3.85 (dd, 1 Η), 3.98 (dd, 1H), 5.72 (m, 1H), 7.60 - 7.79 (m, 3H), 7.90 (m, 1H), 8.62 (s, 1H), 9.27 (m, 1H), 9.38 (s, 1H), 9.55 (m, 1H) 〇? Preparation 56 4-Gas-2-(6-fluoromethane [1,2-8] ° bite -3 · base) shout bite _5_ formic acid ethyl vinegar

a) 2-(6-fluoroimidazo[l,2-a]epyridin-3-yl)-6-oxooxyl,6-dihydropyrimidine-5-carboxylic acid ethyl ester 6-fluoro 0 Rice sulphate [l,2-a]e than bite-3- renegic imine amide hydrochloride (2. 〇202 201130835 gram '9.3 mM, preparation 42b) and 2 · (ethoxy methoxy Diethyl malonate (2.0 g, 9 3 mmol) was added portionwise to a solution of sodium ethoxide in ethanol (21%, 8.14 liters, 18.6 mmol) and the mixture was heated to maintain 6 hours. The resulting precipitate was filtered, washed with ethanol and dried in vacuo at 45 &lt;0&gt;C oven to yield 2.78 g (99%) of title compound. LRMS (m/z): 303 (M+l)+. 'H-NMR δ (DMSO-^): 1.28 (t, 3H), 4.18 (q, 2H), 7.49 (t, 1H), 7.77 (dd, 1H), 8.36 (s, 1H), 8.57 (s, 1H), 10.22 - 10.36 (m, 1H). b) 4-Gas-2-(6-fluoroimidazopyridine)pyrimidine-5carboxylic acid ethyl ester at 2C (2-(6-fluoroimizino[i,2_a]*» than octyl)_4· A suspension of gas oxyphosphorus (2.1 mL, 23 mmol) of pyridine 5-carboxylate (31 mg, 1.03 mmol, preparation 56a) was heated for 2 hours. Excess phosphorus oxychloride was evaporated under vacuum and the residue was poured onto ice. The resulting mixture was neutralized with a 32% aqueous sodium hydroxide solution and extracted twice with ethyl acetate. The water and the brine were combined and aged, __money, and the solvent was removed under reduced pressure to obtain 0.32 g (97%) of the title compound. LRMS (m/z): 321 (M+l)+. Preparation of 57-yl)-4-(1-(5-fluoro"biti-2-(5)-2-(6-fluoroimithia[i,2_a]))ethylamino)pyrimidine-5 -ethyl formate 203 201130835

OEt 4-chloro-2-(6-fluoro miso and (10) ♦ than bite _3_ base) with ethyl acetate (1.3 g, 4.03 mmol, prepared Na) at room temperature, Bite-2-yl)ethylamine hydrochloride (〇72 g, 4〇8 mmol, prepared as described in W〇2006/82392) and diisopropylethylamine (2) 2 mmol = 12.14 mmol) The mixture was decanted under reduced pressure in a mixture of THF (5 gm) and the residue was partitioned between 4% aqueous sodium hydrogen carbonate and EtOAc. The organic layer was separated, washed with water, a brine By reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 acetonitrile-methanol as the eliminator [via 〇.1% v/v citrate buffer] 0% to 1 〇〇 %) Purification of residue to give the title compound (0.63 g, 63%). LRMS (m/z): 425 (M+l)+. h-NMR δ (DMSOO: 1.4 (t, 3H), 1.7 (d, 3H), 4.4 (q, 2ii), 5.5 (t, 1H), 7.3 (m, 1H), 7.4 (m, 2H), 7.7 (dd,1H), 8.5 ^ !H), 8.6 (S, in), 8.9 (s, 1H), 9.1 (d, 1H), 9.7 (dd, 1H) 〇Sj_58 2-(6_fluoroimidazo[ l,2-a]pyridin-3-yl)-4-(pyridin-3-ylmethylamino)pyrimidinecarboxylic acid ethyl ester 204 201130835

According to the experimental procedure as described in Preparation 57, from 4_gas_2_(6_flurimidazo[1,2-a]pyridinylpyrimidin-5-carboxylic acid ethyl ester (600 mg, 1.87 m) Moore Preparation 56b) and Bite-3-Methylamine (190 [mu]L, 1.87 mmol) afforded a solid (71 〇 /0). LRMS (m/z): 393 (M+l)+. ^i_59 2-(6-Fluoroimidazo[i,2_a]pyridine-3-yl)fluoropyridine·2-yl)methylaminopyrimidine-5-carboxylic acid ethyl ester

Prepared from ethyl 4-chloro-2-(6-fluoroimipiro[l,2_a]pyridin-3-yl)pyrimidinecarboxylate (510 mg, 1.59 mmol) according to the procedure described in Preparation 57 56b) and (5-fluoropyridin-2-yl)guanamine (200 mg, 1.59 mmol) afforded a solid (62%). 205 201130835 LRMS (m/z): 411 (M+l)+. Preparation of 60 (5)-2-(6-fluoroimidazo[l,2_a]acridin-3-yl)-4-(l-(4-fluorophenyl)butylamino)pyrimidine-5-carboxylic acid ethyl ester

According to the experimental procedure as described in Preparation 57, ethyl 4-chloro-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidine-5-carboxylate (315 mg, 0.98 m Moor, Preparation 56b) and (S)-l-(4-fluorophenyl)butan-1-amine hydrochloride (200 mg, 0.98 mmol) afforded a solid (92%). LRMS (m/z): 452 (M+l)+. Preparation 61 4-((lr,4/〇-4-(cyanomethyl)cyclohexylamino)-2-(6-fluoroimidazo[l,2-a]0-bit-3-yl) mouth Bite '-5-formic acid ethyl vinegar

206 201130835 According to the experimental procedure as described in Preparation 57, 4_gas_2_(6_Fluoropyrano[1,2-a]. Bite-3-yl) mouth bite 5-ethyl citrate (93 g, 0.29 mmoles [preparation 56b) and 2-((lr,4r)-4-aminocyclohexyl)acetonitrile (51 gram 〇.29 mmol, preparation 47b) afforded solid (66) %). LRMS (m/z): 423 (M+l)+. ΛΑ62 Μ)·3-(3-(2-(6-fluoroimidazolium-α)pyridine_3_yl)_5• nitropyrimidin-4-ylamino) brigade bite-1-yl)_3_ Side oxypropionitrile

a) (and)-3-(2-(6-fluoro-salt and n-bito-3)5-nitro-4-ylamino) brigade 1-carboxylic acid tert-butyl vinegar at room temperature 3-(4-Ga-5-nitropyrimidin-2-yl)_6_gas_. Sit and [u-bite (10) mg, (four) millimolar, prepared) 4^, H-aminopiperidine-1-decanoic acid tert-butyl ester (83 mg, 〇41 mmol) and diisopropyl B A mixture of the amine (13 G microliters, 〇. 75 mmol) in tetrahydro-seven (ι) was overnight. Evaporation solvent was partitioned between chloroform and 4% aqueous sodium bicarbonate. The organic layer was separated, (4), EtOAc (EtOAc m.) : 458 (M+l)+ wi scented saliva and [1,2_iZ] bite ·3-base)_5 determinate _AL (Brigade -3-yl) gnace-4-amine trifluoroacetic acid (775 micro l, 丨〇. i millimoles) added to _ _ _ [1,2-β] π than bite base -5 · nitro quinone + amide amine bite small milligrams '(four) millimoles, preparation 62a) The second gas, =) solution + and the mixture obtained at the temperature of the mixture until the reaction element is formed. The solvent is partitioned and the residue is partitioned between (2) and a 2 N gas oxidizing aqueous solution. The title compound was obtained in the form of a yellow solid (78%) as a yellow solid. LRMS (m/z): 358 (M+l)+ C) (Λ)-3·(3-(2-(6-fluoro-salt and like but 唆_3·yl)-5-based acridine -4-ylamino)piperidine-I-yl)_3_sideoxypropionitrile, according to the experimental procedure as described in Preparation 34c, by (Fantasy-2-(6·Fluorometer sit and [1,2 ]] than bite _3_ base) nitro good (nchen bite j base) mouth 唆 _4 · amine (just mg ' 〇. 39 millimoles 'preparation must) and 3- [(2,5_ two sides) Oxypyrrole-1-yl)oxyloxypropanenitrile (86 mg, 〇47 mmol, prepared as described in BE 875054 (A1)) gave a yellow solid (32 〇 /.). Chromatography (from Waters c_18 dioxo, water / 1:1 acetonitrile _ methanol as a dissolving agent [0.1% v/v formic acid buffer] 〇% to 1%) was used to purify the crude product. LRMS (m/ z): 425 (M+l)+ NMR δ (CDC13): 1.7-2.3 (m, 5H), 3.1-4.0 (m, 208 201130835 (m, 1H), 7.8 (m, 1H), 8.5 (m , 1H), 5H), 4.3-4.6 (m, 2H), 7.4 8.7 (m, 1H) 9.8 (m, 1H) 〇Reserve 63 5-cyclopropyl-2-(6-fluoro-salt [12 _ _ _3 · base) compared to -4 alcohol

A butyl bell (1.62 ml of 2.5 Μ 吱 hydrogen oxime solution, 4.05 mmol) was added to diisopropylamine (52 (microliters, 3.7 mmol) without water under an argon atmosphere at _2 °C. Tetrahydrofuran (1 〇 ml) solution. The resulting mixture was stirred for 45 minutes, then cooled to 耽 and at this temperature] 2-cyclopropylacetic acid was added slowly (384 mg, 3% millimolar, female (four) prepared) tetrahydro-seven (5) After the solution stems and the next 3 〇 / knife knives, add formic acid ethyl vinegar (270 μl, 3.36 i of tetrahydrofuran (5 liters) solution and maintain the inside after 1 hour' then rise to the chamber ^ 0 6-fluorine嗤 嗤 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( And stirring at room temperature under stirring for 2 hours under microwave irradiation. Under vacuum: except: in (10) solution in water, by adding 2 N _water-soluble wire; and to pHH 209 201130835 filtration The precipitate was washed with water and diethyl ether and dried to give the title compound (yield: EtOAc (m/z): 271 (M+l)). :0.8 (m,4Η), 1.9 (s,1Η), 7.6 (s, 1H), 7.8 (s, 1H), 7.9 (s, 1H), 8.7 (s, 1H), 9.9 (s, 1H), 12.8 (s, 1H) Preparation of 64 (Λ)-5-cyclopropyl-2-(6- Shu imidazo] 1,2 · β "specific-3-yl) -7V- (piperidin-3-yl) pyrimidin-fighting amine

a) (and cyclopropyl-2-(6-fluorobenzoate and [1,2_α]0 to bite_3_yl)-l-pyridin-4-ylamino)piperidine-1-carboxylic acid tert-butyl ester according to Preparation of the experimental procedure described in 5a, from 5-cyclopropyl-2-(6-fluoroimidazo[1,2-«]pyridin-3-yl)pyrimidin-4-ol (85 mg, 0 31 mmol) Preparation 63) and (and) _3_amine decyl citrate tributyl vinegar (188 g, 0.94 mmol) gave an oil. The crude product was used in the next step without further purification. '' LRMS (m/z): 453 (M+l)+. b) (and)-5-cyclopropyl-2_(6-fluoroimidazopyridyl)K/V-(Brunken-3-yl) blasting _4·amine 210 201130835 Difluoroacetic acid (121 micro Liter, 157 millimoles) added to (λ)_3·(5_cyclopropyl-2-(6-fluoroimidazo[丨,^^]pyridine-3-yl)pyrimidin-4-ylamino)piperidine- The solution of the second butyl phthalate (preparation 64a) in dioxane methane (2 ml) was stirred at room temperature overnight. The solvent was evaporated and the residue dissolved in water and basified with saturated aqueous potassium carbonate. The organic phase was washed with EtOAc (EtOAc) EtOAc (EtOAc) l)+. H NMR δ (CDC13)·· 0.6 (m, 2Η), 1.0 (d, 2Η), 1.5-2.0 (m, 6H), 2.8 (m, 3H), 3.2 (dd, 1H), 4.3 (m,ih), 5.8 (d,lH), 7.2 (m,1H),7.6 (dd, 1H),8.0 (s,1H),8.5 (s,1H) l〇.〇(dd,lH) , M Preparation 65 4_Chloro-2_(6-fluoroimidazoacridin-3-yl)pyrimidine j-carbonitrile

a) 2-(6------------------------------------------------------------------------------------- And [1,2-β]acridin-3-carbonylindoleamine (i.oo g, 4 66 mmol, preparation 42b) and (2)_2-cyano-3-ethoxyacrylic acid The ester (123 grams, 7.27 millimoles) in a suspension in ethanol (15 ml) and at 211 201130835 卯. The resulting mixture was stirred in a sealed tube under argon for 3 hours to evaporate the solvent and (4) the residue was dissolved in a pure imitation towel. The crude product was purified by trituration with q: </ br> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> . · Mock LRMS (m/z): 256 (M+l)+. ^ΝΜΚδ (CDCl3): 7.5 (m, lH), 7.8 (dcl5lH) 1H), 8.3 (s, 1H), 10.2 (dd, 1H). ), 8.2 (s, b) 4-gas-2-(6- oxazolo[l,2·bite _3-yl) 嚷 at 110 ° C, such as 奋米嗤 and (10) ♦ than d- A guessing ·5_carbonitrile (9) mg, (iv) millimolar, prepare 65a) H^ base dish (0.5 ml) float for 90 minutes, then pour into the mixture. The aqueous solution was basified with aqueous sodium hydroxide solution and taken up with ethyl acetate and ice. The organic layer was washed with EtOAc (EtOAc m. The ',, w complex' produced LRMS (m/z): 438 (M+l)+. Insect NMR δ (CDC13): 7.4 (m, 1 Η), 7.8 (dd 1H), 8.9 (s, 1H), 9.8 (dd, 1H). 8*8 (s, Preparation 66 (^)-2-(6-fluoroimidazo[1,2-«]pyridine_3_ylpiperazin-5-carbonitrile-ylamino)

CI

212 201130835 a) (j?)-3-(5-fluoro-based 2-(6-fluoro-sodium benzo-[12♦ 唆-4-ylamino) brigade bite 1-carboxylic acid tert-butyl vinegar (8) collar Slightly 唆-1· citrate third vinegar (40 gram, 〇 2 () millimolar) and diisopropylethylamine (65 μl, 〇.37 mM 4 氯 2 _ 2, (6, Saliva and [U_♦ than bite base} spray bite d A yield 'mg' 0.18 house Moer, preparation (four)) tetrahydrogen ^, residue knife with Teflon and 4% sodium bicarbonate aqueous layer organic layer, with Wash with brine, dry over MgSO4, EtOAc (EtOAc) elute EtOAc (EtOAc) However, according to the experimental procedure described in Preparation 5b, (/0-3-(5-cyano-2-(6)) was prepared according to the experimental procedure described in Preparation 5b. -Fluoroimidazo[1,2-α]pyridine-3-yl)pyrimidin-4-ylamino)piperidine-hydrazinic acid tert-butyl, (80 mg, 016 mmol, preparation 66a) afforded solid (54 %) The crude product obtained was used in the next step without further purification. LRMS (m/z): 338 (M+l) +. Preparation 67 - (Fantasy-2#-gasimidazolyl) acridine_ 3_yl)-4-(Bistidine·3_ylamino)pyrimidine-5-carbonitrile 213 2 01130835

Sodium carbonate (190 mg, 1.79 mmol) was added to 6-fluoroimipiro[1,2-α]pyridine-3-carbonylindoleamine (330 mg, 1.49 mmol, Preparation 42b) and (6) -3-(dimethylamino)·2_(methylsulfonyl)acetic acid ethyl vinegar (768 mg, 3.58 mmol, prepared according to US2004/6743798) in decyl alcohol (15 ml) and water (0.5 ml) The resulting mixture was heated to reflux overnight. The solvent was evaporated and the title compound was crystaljjjjjjjjjj LRMS (m/z): 460 (M+l)+. !H NMR δ (DMSO-禹): 3.2 (s, 3Η), 7.6 (m, 1Η), 7 8 (dd, 1H), 8.4 (s, 1H), 8.6 (s, 1H), 10.1 (dd, 1H). Preparation 68 (and)-2-(6-Fluorine and [l,2-ii]〇 咬-3-yl)-5-(methylisophilic)-Λ"·(piperidin-3-yl) Pyrimidine-4-amine

214 201130835 a ) (Λ)-3-(2-(6-Azamidazopyridine-3-yl)_5_(methylsulfonyl) gnaca-4-ylamino) brigade bite_ι·carboxylic acid third vinegar According to the experimental procedure as described in Preparation 5a, (and)_2_(6_Fluoro miso[1,2_α] bite I base)_4_(pyridinylyl)amino) 22 mg, 0.71 mmol, preparation 67) and (and) _3_aminopiperidine-1-decanoic acid terpene vinegar (430 mg, 2.15 mmol) obtained (29% yield) solid . The crude product was purified by flash chromatography (0 to 1% hexanes /EtOAc) LRMS (m/z): 491 (M+l)+. b) (Λ)-2-(6-fluoroimidazo[i,2_tf]„bipyridine·3_yl)_5_(methylsulfonyl)-?V-(Big-3-yl) bite-4 -amine according to the experimental procedure described in Preparation 5b, by 3_(2_(6_fluoroisoxazole[1,2 god than biting-3-yl)-5-(曱 酿 酿)) Amino) sent a small amount of formic acid tert-butyl (10) mg '0.20 mmol, prepared to give a solid (38%). The crude product was used without further purification, LRMS (m/z): 391 ( M+l)+. Step number: 69 Piperidin-3-ylamino) (Λ)-2-(6-fluoroimidazolium 1,2-&lt;ι) "Acridine-3-yl" Pyrimidine- 5-ethyl formate

215 201130835 a) (and Μ-(ι-(t-butoxycarbonyl) piperidine_3.ylamino)·2_(6_like miso[1,2_α]pyridine·3·yl)pyrimidine_5 _ ethyl formate technique as described in Preparation 66a, by 4-chloro-2-(6-fluoroimidazo[1,2呐pyridin-3-yl)pyrimidine-5-carboxylic acid ethyl ester (83〇 </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; (The crude product was purified from Waters C_18 cerium oxide, water/1:1 acetonitrile _ methanol as a dissolving agent [0.1% v/v citric acid buffer] 〇% to 1%). LRMS (m/z ): 485 (M+l)+. b) (and)_2_(6·fluoroimidazo[1,2-«]pyridyl)-4-(pyridin-3-ylamino)pyrimidine-5-carboxylic acid Ethyl ester according to the experimental procedure described in Preparation 5b, from (and) _4·(ι_(Tertixobutoxy) σ 咬-3-ylamino)-: 2-(6-fluoroimidazo[1] Ethyl 2-(?)-indolozol-3-yl)pyrimidine-5-carboxylate (840 mg, 1.73 mmol, Preparation 69a) gave solid (93%). The crude product was used in the next step without further purification. LRMS (m/z): 385 (M+l)+.丨H NMR δ (CDC13): 1.4 (t, 3H), 1.6-2.1 (m, 4H), 2.0 (d, 1H), 2.8-2.9 (m, 3H), 3.3 (dd, 1H), 4.3 (m , 1H), 4.4 (q, 2H), 7.3 (m, 1H), 7.7 (dd, 1H), 8.6 (m, 2H), 8.9 (s, 1H), 10.0 (dd, 1H). , Preparation 70 3-(4_气methoxy-mouth bite_2_基)_6_氡珠唾[and Yiwaibi bite 216 201130835

Alcohol a) 2-(6 primordial [1, 2♦ than heart-based) _5 • methoxylated winter ethyl formate (57 〇 microliters, 7 ethyl acetate (53. microliters, 4.52 亳: Ear) ~ and 2_ methoxy mg 60% mineral oil suspension, 5 〇〇, '&quot; to 虱 纳 (120 liters) suspension, and at room temperature four thief (2 mM sterol) Sodium sterol solution (25%, i material barrier. Then add [U♦ 岭3·魏亚胺 醯amine α (8 ml) and 6 · odor 嗤 and 42b) isopropyl alcohol (2 ml) solution ^ Moer's were maintained for 2 hours after preparation, then heated to reflux with water and the addition of acetic acid until the formation of the product was dissolved in the polyester and dried to yield 460 mg (39%) of a color solid. Wash LRMS (m/z) with water: 261 (M+l) + 'compound. 丨H NMR δ (DMSO-can 3 8 (7·7 (s, 1Η), 7.8 (m, 1H), 8.6 (s, 1Η) ^ 3ίί)' 7.6 (m,1H),

V 1H). · 8 (called 1H), 12.6 (bs, you (4_ gas _5_ methoxy sulfonate according to the experimental procedure described in Preparation 65b _, oxazolidine, 1, 2 ^) pyridinium, 2- noisy Bis-pyridine·3_Α)_5·ρ-oxypyrimidine- 4• alcohol, from 2-(6-fluoroimidazole, preparation 70a) gave 410 mg (61 〇 / > 630 mg, 2.42 mmol) of the title compound. 217 201130835 LRMS (m/z): 279 (M+l) +. Preparation 71 〇R)-2-(6-fluoroimidazo[1,2-&lt;1] acridine-3-yl)-5-曱oxy-7V-(piperidin-3-yl) whistle-4-amine

a) (Λ)-3·(2-(6-fluoroimidazo[l,2-fl]acridin-3-yl)-5-methoxypyrimidin-4-ylamino) brigade bite-1 - formic acid second butyl vinegar according to the experimental procedure as described in Preparation 66a, from 3-(4-a-5-methoxypyrimidin-2-yl)-6-fluoroimidazo[1,2-α]indole Acridine (410 mg, 1.47 mmol, Preparation 70b) and (3 butyl 3-aminopiperidine-1-decanoate (295 mg, 1.47 mmol) afforded (41% yield) solid The reaction mixture was stirred overnight under reflux by reverse phase chromatography (C-18 from Waters, water/1:1 acetonitrile-nonanol as the dissolving agent [with 0.1% v/v formic acid buffer] 0% to 100%) Purified crude product. LRMS (m/z): 443 (M+l) + NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.0 (m, 4H), 3.4- 3.7 (m, 4H), 3.9 (s, 3H), 4.2 (d, 1H), 5.5 (bs, 1H), 7.2 (m, 1H), 7.7 (dd, 1H), 7.8 (s, 1H), 8.4 (s, 1H), 9.9 (dd, 1H). b) (i〇-2_(6-fluoroimidazo[l,2-ii]acridin-3-yl)-5-decyloxy-TV-( BTS-3-yl) mouth bite-4-amine 218 201130835 and nSf prepared experimental procedure '(10)), 3-(2♦ fluoro* sitting second sputum (300 mg, 0.68 mmol, system ( 91%). Without further purification, 7^) can be used, and LRMS (m/z): 343 (M+l)+ is added. Step Λ Preparation 72 3-(4,6·Di-pyrimidin-2-yl)-cardiofluoroimidazole Pyridine

a) 1(6·fluoroimidazopyridine-3-yl)pyrimidine-46diol 6-fluoroimidazo[1,2-pyridinium carbonyl hydrazide decylamine (7.0 g, 32.6 亳 Mo under 〇C) Preparation of 42b) and diethyl malonate (9 9 ml, 65.2 mmol) added to a solution of sodium (2 25 g, 97 8 mmol) in methanol* (14 g mL) at room temperature The resulting mixture was scrambled for 4 hours. The solvent was evaporated and the residue was dissolved in 2 (8 mL) water. The resulting solution was stirred at room temperature for 1 hour' followed by acidification with 5NHC1 until a broad-color solid. The residue was washed with water and EtOAc (EtOAc) (EtOAc) !ΗΝΜΚ δ (DMSO-^): 5.3 (bs, 1Η), 7.6 lm 7.9 (dd, 1H), Ο (bs, 1H), 10.1 (dd, 1H), ^ 5 (bs, ih)' to 219 201130835 (bs, 1H). b) 3-(4,6-two gas 唆 唆 私 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 A suspension of oxygenated phosphorus (3〇 New) of _4,6_ monool (4.28 g, Π.38 mmol, preparation 72a) was refluxed overnight. Evaporation of excess ferric phosphorus and distribution of the crude material to water and dichlorobenzene Water and brine organic phase, dissolved in sodium sulfate and removed under reduced pressure (67%) LRMS (m/z): 283 (M+l) + lH surface δ (CDCl3): 7.2 ( s, 1H), 7.4 (m, 1H), 7.8 (dd 1H), 8.7 (s, 1H), 9.8 (dd, 1H). Preparation 73 (J?)-3-(6-gas-2-(6) _Fluoroimidazo[12呐pyridine-3-yl)pyrimidine-4-ylamino) brigade bite-1-anthracene third

Add W-3-Amino-based small formic acid third Tg| (141 g, 7 () 4 mmol) to ^ ° 唆 (1.0 g '3.53 mmol, prepare 7 ethanol (6 〇) The resulting mixture was heated to reflux overnight. The solvent was evaporated and the crude material was partitioned between water and water. The organic phase was separated, washed with water </ RTI> </ RTI> <RTIgt; Dioxane to 94:6 dichloromethane / decyl alcohol) Purified residue &amp; mp mp (yield: EtOAc) M+l)+ 1,5'2-2 (m, 5H), (called 1H), 7.7 (dd, ]H NMR δ (CDC13): 1.5 (s,9H), 3.3-3.8 (m, 4H) , 5.2 (s, 1H), 6.2 (s, 1H), 7.3 1H), 8.6 (s, 1H), 9.8 (dd, 1H). Preparation 74 CR)-2-(6-fluoro miso and [l, 2-a]°° bite _3 base)-6-(1 ugly-1,2,4-triazin-1-yl) spuramine-based) is called piperidine-3-

a) (Λ)-3-(2-(6-fluoroimidazolyl-saltyl-1)-glycine-4-ylamino) brigade bite-1-carboxylic acid third dinning', 4 will be 1 ugly - 1,2,4-triazole (77 mg, 1.11 mmol) Mountain planer (364 mg, 丨.12 mmol) was added to (3_(6_气_, acid oxazolo[1,2-α) a solution of dipyridyl methacrylate (100 mg, 0.22 mmol, preparation 73) in xylylenediamine (3 ml) in pyridine-3-yl)pyrimidin-4-ylamino)piperidinium carboxylic acid 13 (the mixture obtained by heating under TC i =, formazan is then allowed to stand at room temperature overnight. Evaporating the solvent and treating the residue with water, the precipitated white solid is filtered, washed with water and dried to give 99. See (92〇/〇) 221 201130835

LRMS (m/z): 480 (M+l)+ 】H NMR δ (CDCUY •1 (m,4H), 1H), 8.1 (s, H NMR δ (CDCW: 1.5 (s, 9Η), 1.6- 2 3.4-3.9 (m, 5H), 6.7 (s, 1H), 7.3 (m, iH), 7 7 (m 1H), 8.6 (s, 1H), 9.2 (s, 1H), 9.8 (s, 1H) ) : · '

Warm down overnight. Then trifluoroacetic acid (80 μl) was added and after completion of the reaction, the reaction mixture was diluted with a methane and water. The aqueous phase was separated and verified by slow addition of a saturated aqueous solution of carbonic acid and extracted several times with a gas pattern. The combined organics were washed with EtOAcqqqqqqqqq LRMS (m/z): 380 (M+l)+ !H NMR δ (CDC13): 1.6-2.0 (m, 5H), 2.8-3.2 (m, 4H), 5.9 (s, 1H), 6.7 (s , 1H), 7.3 (m, 1H), 7.7 (dd, 1H), 8.1 (s, 1H), 8.6 (s, 1H), 9.2 (s, 1H), 9.8 (dd, 1H) ° Preparation 75 (and )-2-(6-fluoroimidazopyridine pyridine)_6_(heart methylpiperidin-1·v group)-iV-(Big -3-yl) spur bit-4_amine 222 201130835

a ) (/?)-3-(2-(6- 嗤味嗤和u,2·啦 bit_3_基)·6 (4 methyl 嗓·_1-yl) mouth bite-4-ylamine Base) bite · ι_carboxylic acid third butyl according to the procedure described in Preparation 74, from w_3_(6un carbazolo[1,2-micropyridin-3-yl)- phenanthylamino) Preparation of pyridine + tert-butyl formate (1 mg, 0.22 mmol, Preparation 73) and μMethylpiperazine &amp; 2 〇 microliter, 1.12 mmol. The product was purified by flash chromatography (yield of hexanes to pi.sub.2). LRMS (m/z): 511 (M+l) + NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 5H), 2 3 (s, 3H), 2.5 (m, 4H) , 3.2-3.9 (m, 8H), 4.7 (d, 1H), 5.4 (s '1H) 7.2 (m, 1H), 7.6 (dd, 1H), 8.4 (s, 1H), 9.8 (dd, 1H) . ' b ) (Ι?)-2·(6-azamidazo[1,2-α]pyridin-3-yl)-6•...methyl bromo-1-yl)-Λ"-(piperidine- 3-yl)pyrimidine-4-amine is prepared according to the procedure described in Preparation 74b from (i--3-(6-fluoroimidazo[1,2-carbidin-3-yl)-6-( 4-methyl α-Chenazine-1-yl)-pyridylamino) butyl 1-carboxylic acid tert-butyl ester (68 mg, 0.13 mmol, preparation 75a) and trifluoroacetic acid (51 μL, 0.66) The title compound (55 mg, 1%) was obtained as a white solid, which was used in the next step without purification. 223 201130835 LRMS (m/z): 411 (M +l)+ 'H NMR δ (CDC13): 1.5-2.0 (m, 5H), 2.3 (s, 3H), 2.5 (m, 4H), 2.6-2.9 (m, 3H), 3.2 (dd, 1H) , 3.6 (m, 4H), 3.8 (bs, 1H), 5.0 (d, 1H), 5.4 (s, 1H), 7.2 (m, 1H), 7.6 (dd, 1H), 8.4 (s, 1H), 9.9 (dd, 1H). Preparation 76 (i?)-4-(6-(l-(2-Aza-ethyl-branched) brigade-3-ylamino)-2-(6-acidazole) [l,2-ii]pyridin-3-yl)pyrimidin-4-yl)piperazine-1-carboxylic acid benzyl ester

a) (1?)-4-(6-(1-(2nd-butoxy-reactive) brigade-3-ylamino)-2-(6-azamidazo[1,2峋pyridine-3- Phenylpyrimidin-4-yl)piperazine-1-carboxylic acid benzyl ester Piperazine-1-indole benzoate (540 μL, 2.79 mmol) was added to (i?)-3-(6- Gas-2-(6-gas σ sitting and [1,2-fl]π ratio -3-yl) ♦ -4-amino-amino) piperidine-1-decanoic acid tert-butyl ester (250 mg, The resulting mixture was heated in a solution of 73) in decylpyrrolidone (2 ml) and heated under microwave irradiation at 130 °C for 2 hours. The reaction mixture was partitioned between water and 224 201130835 dioxane and the organic phase was separated, washed with water and brine, dried over sulphuric acid and evaporated. The product was purified by flash chromatography eluting EtOAc (EtOAc) LRMS (m/z): 631 (M+l) + NMR δ (CDC13): 1.4 (bs, 9H), 1.6-2.1 (m, 5H), 2.4 (m, 4H), 3.1-3.9 (m, 8H) ), 4.8 (bs, 1H), 5.1 (s, 2H), 5 4 (bs, 1H), 7.2 (m, 1H), 7.3 (m, 5H), 7.6 (dd, 1H), 8.4 (s 9.8 ( Dd, 1H).,,(1)), b) (i?)-4-(2-(6- defeated 叩-中中中咬·3_基)_6 (tracelamine) bite-4 -Based on -i-methyl benzoate &quot; and (and (di-carbonyl)piperidin-3-ylamino)-2-(6-fluoroimidazolyl) according to the procedure described in Preparation 74b [1,2-Synylpyridinylbutoxy-4-yl)piperazine-indole-formic acid benzyl ester (339 mg, 〇54 mmol, pyrimidine 76a) and trifluoroacetic acid (4 丨 4 μl, The title compound (238 mg, 84%) m. One step of purification is obtained for the next step. LMS (m/z): 531 (M+l) + lR NMR δ (CDC13): 1.7-2.0 (m, 4H), 2 3_2 5H), 3.2-3.8 (m, 9H), 5.1 ( d, 1H), 5.2 (s, 2H), 5.4 (s m9/m, (m, 1H), 7.3 (m, 5H), 7.6 (dd, 1H), 8.4 (s, 1H), 9.9 (dd) , 7.2 Ο ΜΜ-(6·(ι-(2·cyanoethyl) benzylidene)·24Η) ° Imidazo[1,2-β]pyridine-3-yl)eridine-4 - yl)pyrazine small formic acid benzoate fluorene 3-[(2,5-di- oxypyrrolidine fluorenyl) oxy]_3_ side oxygen ^ 225 201130835 (123^g, 0.68亳莫耳, as in BE875〇54 (A1) and triethylamine (94 μl, 〇·67 mmol) added to (force _4 m sit and [1,2_α]pyridine base)_6_(〇辰啶_3_ylamino)pyridin-1-decanoic acid yoke (238 mg, 〇.45 mmol, prepared as described in ΒΕ 875054 (Α1)) 〇·67 millimoles) added to α _4_(2_(6·Fluoro-yl)° bottom. Qin 0.45 mmol, prepare 76b) of the simmering (10 ml) solution towel and obtain the mixture at room temperature. The solvent is then evaporated and the residue is partitioned between water and gas. The 1 layer was separated, washed with water and brine, dried over magnesium sulfate and evaporated. Purification of the crude material by flash chromatography eluting EtOAc (EtOAc) LRMS (m/z): 598 (M+l)+, H NMr δ (CDC13): 1.7-2.2 (m, 4H), 3.3-3.8 (m, 14H), 4.1-4.8 (m, 2H), 5.2 (s, 2H), 5.5 (s, 1H), 7.2 (m, 1H), 7-4 (m, 5H), 7.7 (m, 1H), 8.5 (d, 1H), 9.8 (m, 1H) ° ^t_77 (Λ)-2-(6-fluoroimidazo[l,2-tf]e-pyridyl-3-yl)-6-(N-morpholinyl)-?V-(piperidin-3-yl) Pyrimidine-4-amine

a) (Λ)-3-(2-(6-fluoroimidazo[1,2·φ-pyridin-3-yl)_6·(Ν-morpholinyl)pyrimidin-4-ylamino)piperidine- 1-butylic acid tert-butyl ester according to the procedure described in Preparation 76a, from 0)-3-(6-chloro-2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)pyrimidine- 4-Aminoamino)piperidine-1 -carboxylic acid tert-butyl 226 201130835 The next day (100 mg '0.22 mmol' preparation 73) and morpholine (1 〇〇 microliter, 1.12 mmol). The crude product was purified by flash chromatography eluting elut elut elut elut elut elut elut elut LRMS (m/z): 498 (M+l) + H NMR δ (CDC13): 1.4 (s, 9H)s 1.6-2.1 (m, 5H), $3.3 (m, 4H), 3.6 (m, 4H) , 3.8 (m, 4H), 4 8 (bs, 1H), 5 4 s, 1H), 7.2 (m, 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.8 (dd, 1H) . b) (and)-2-(6-fluoroimidazo[l,2-e-bipyridyl_3_yl)_6_(N•morpholinyl)-indole "-(piperidin-3-yl)pyrimidine- 4-amine according to the procedure described in Preparation 74b 'from fluoroimidazo[1,2-β]pyridine-3-yl)-6-(indolyl-morpholinylpyrimidin-4-ylamino)piperidine _ Prepared as a white solid (68 mg, 100%), which can be used in the next step without further purification. LRMS (m/z): 398 (M+l) + !H NMR δ (CDC13): 1.6-2.0 (m, 4H), 2.7-3.0 4H), 3.2-3.4 (m, 2H), 3.6 (m, 4H), 3.8 (m, 4H), 5.1 (bs, 1H), 5.4 (s, 1H), 7.2 (m, 1H), 7.6 (dd ,1H), 8.4 (s,1H), 9.8 (dd, 1H) 〇' Preparation (Λ)-2-(6-fluoroimidazo[l,2-ii] cycline·3·yl)y〆! Methyl(piperidin-3-yl)pyrimidine-4,6-diamine 227 201130835

a) (i?)-3-(6-(dimethylamino)-2-(6-fluoroimidazo[1,2-ίΐ]η-pyridin-3-yl)pyrimidin-4-ylamino) Piperidine-1-carboxylic acid tert-butyl ester according to the procedure described in Preparation 76a, containing (/^-3-(6-chloro-2-(6-fluoroimidazo[1,2-α]pyridine-3) -yl)pyrimidin-4-ylamino)piperidine-1-decanoic acid tert-butyl ester (100 mg, 0.22 mmol, preparation 73) and didecylamine (0.56 ml 2 decyl alcohol solution, 1.12 m) Preparation of dimethyl decylamine (2 ml). The crude product was purified by flash chromatography (dichloromethane to 92:8 methane / methanol) to give 59 mg (49%) The title product is a solid. LRMS (m/z): 456 (M+l) + ]H NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 4H), 3.2 (s, 6H) , 3.1 (m, 1H), 3.6-3.9 (m, 4H), 4.7 (bs, 1H), 5.3 (m, 1H), 7.2 (m, 1H), 7.6 (dd, 1H), 8.5 (dd, 1H) ), 9.9 (dd,1H). b) (i?)_2_(6-fluoroimidazo[l,2-ii]"pyridin-3-yl)-A^TV4-dimethyl (Brigade bite-3 -based) 4-,6-diamine according to the procedure described in Preparation 74b, from (i?)-3-(6-(dimethylamino)-2-(6-fluoroimidazo[1, 2-4 acridine-3-yl)pyrimidin-4-ylamino)piperidine-1-carboxylic acid Tributyl (59 mg, 0.13 mmol, prepared 78a) and trifluoroacetic acid (50 [mu] L, 0.65 mmol) was prepared. The title compound (46 mg, 100%) elute LRMS (m/z): 356 (M+l)+ Preparation 79 W-2_(6-fluoroimidazo[1,2-&lt;!]pyridin-3-yl)-y-(2-(N- Morpholinyl)ethyl hTV6-(piperidine-3-yl)pyrimidine_4,6-diamine

a) (Λ)-3·(2-(6·Fluoropyrano[ι,2·β]π than indol-3-yl)-6-(2-(N-morphinyl)ethylamino) Mouthyl cis- 4-ylamino) benzyl pyridine tricarboxylic acid tert-butyl ester according to the procedure described in Preparation 76a, containing (〇-3-(6-chloro-2-(6-fluoroimidazo[1,2] -α]° than bite _3_ base) mouth bite-based amino group) shouted 1-carboxylic acid third vinegar (100 mg, 0.22 mmol, preparation 73) and 2-(Ν-?你基基) B Amine (147 μl '1.12 mmol) of #•methyl a was prepared in hexamidine (2 mL). The reaction mixture was heated under microwave irradiation at 130 ° C for an hour, then heated at MOt for an additional 4 hours. The crude product was purified by flash chromatography eluting eluting elut elut elut elut elut elut elut elut (M+l)+Plus 5 (CDCl3): 1.4 (s, 4H), 2H), 1.6-2.1 (m, 2H), 2.5 (m, 2H), 2.6 (m, 1H) 6 (m, 5H ), 4.7 (d, 1H), 5.3 (bs, 1H), 7.2 (dd, lH)' 7 / 3·4·3.8 (m, (s, 1H), 9.9 (dd, 1H) ° ' · (dd , speak), 8.5 229 201130835 = two: the second) ~ [,, bite -3- Η · (2 · (Ν • 琳琳基) ethylamine) The title compound (45 mg, the title compound was obtained as a color solid) (yield: m.p. %), which can be used in the next step without purification = ν LRMS (m/z): 441 (M+l)+

MMJO (and)-2-(6-fluoroimidazolium pyridine-3-yl)_¥_(2methoxyethyl HV6-(dentate _3·yl) bite _4,6-diamine

a) (and) -3-(2·(6·fluoroimidazo[1,2_tf]nbipyridine:yl)_6_(2-methoxyethylamino)-l-pyridin-4-ylamino) The third butyl ester was prepared according to the procedure described in Preparation 76a, containing (8)-3-(6-chloro-2-(6-|t miso[1,2-α]n-pyridin-3-yl) Iridine-4-ylamino) british _ι_carboxylic acid terpene vinegar (250 mg, 0.56 mmol, preparation 73) and 2 methoxyethylamine (210 mg, 2.80 mmol) iV- Preparation of fluorenyl pyrrolidone (2 ml). The reaction mixture was heated under microwave irradiation at 14 ° C for 2 hours. The crude product was purified by EtOAc EtOAc EtOAc: LRMS (m/z): 486 (M+l)+ !H NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.0 (m, 4H), 3.2 (bs, 2H), 3.4 (s, 3H) ), 3.5-4.1 (m, 6H), 4.7 (bs, 1H), 5.0 (bs, 1H), 5.3 (bs, 1H), 7.2 (m, 1H), 7.6 (dd, 1H), 8.4 (s, 1H), 9.9 (dd, 1H). b) (and) -2_(6-fluoroimidazo[l,2-d]pyridin-3-yl)methoxyethyl j-TV6- (spotted-3-yl) bite-4,6-two The amine is prepared according to the procedure described in Preparation 74b from (and)-3-(2-(6-fluoroimidazo[1,2-(3]° ratio -3-yl)-6-(2-oxime 1 ethylamino) ringing -4-ylamino) brigade bite-1-butyl citrate (156 mg, 0.32 mmol, preparation 80a) and trifluoroacetic acid (124 μl, 1.61 mmol) The title compound (123 mg, <RTI ID=0.0></RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; (CDC13): 1.6-2.0 (m, 5H), 2.6-2.8 (m, 2H), 2.9 (m, 1H), 3.2 (dd, 1H), 3.4 (s, 3H), 3.5-3.7 (m, 4H ), 3.7 (bs, 1H), 5.0 (bs, 2H), 5.2 (s, 1H), 7.2 (m, 1H), 7.6 (dd, 1H), 8.4 (dd, 1H), 10.0 (dd, 1H) Preparation 81 gas-2-(6-odorant and [l,2-d]n ratio bit-3-yl) mouth bite-4-yl) pyrrolidine-2-carboxylate 231 201130835

F

Cl +

(5)-2-(Methoxycarbonyl)pyrrolidinium chloride (3 mM) and triethylamine (607 μl, 4.35 mmol, 2·37 II gas, 2 boat 6 - Fluorine material is similar to rushing (four) (, 5^ to 3, preparation 72b) in ethanol (20 ml) suspension ^ ^ to reflux for 3 hours. Evaporation off and make _ matter ^ water and gas imitation H The layers, the deciduous and the ruthenium, dried over magnesium sulphate and hexanes to give _mg (yield: 81%) of the title product. l) + , H NMR δ (CDC13): 2.1-2.4 (m, 4H), 3&gt;4.3&gt;7 (m? 2H), 3.8 (s, 3H), 4.8 (dd, 1H), 6.3 (s, iH), 7.3 (m, 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.7 (s, 1H) ° Preparation 82 (5)-1-(2-(6-fluoroimidazo[Ha] Pyridine _3_yl)6(w piperidin-3-ylamino) shouting -4-yl) ι» than slightly biting _2_carboxylic acid 232 201130835

a) (and)-3-(2-(6.fluoroimidazo[ΐ,2-β]pyridine-3-yl) winter (tetra)_2_(methoxycarbonyl)pyrrolidin-1-yl)pyrimidine_4_yl Amino) piperidine·j•decanoic acid tert-butyl ester (the third derivative of phantom_3_aminopiperidine-1-decanoate (8 〇〇 mg, millimolar) was added to (&lt;S&gt; 1 -(6-Gas-2-(6-fluoroimidazo[丨,2_β]pyridine-3-yl)pyrimidin-4-yl)pyrrolidine-2-carboxylic acid oxime ester (6 mg, 16 〇 〇 The resulting mixture was heated in a suspension of ethanol/preparation 81) in ethanol (5 ml) and heated under microwave irradiation for 16 hours. The solvent was then evaporated and the residue was partitioned between water and gas. And the salt water was dried over sulphuric acid and the solvent was evaporated. The crude product was purified by flash chromatography (yield to hexane: chloromethane / methanol) to give (10) mg (16%) of title. (m/z): 540 (M+l)+ b) (5)-1_(2·(6· 咪 唾 并 n n n n 3 3 3 3 3 )) Bite-4-yl)"»Bilo bite_2_formic acid methyl vinegar according to the procedure described in Preparation 74b, from (2_(6_Fluorophenanthranyl)-based bite·1_capric acid Third butyl ester (14 mg, The title compound (1 〇 3 mg, 9 〇 %) was obtained as a pale yellow solid, 233, 2011 835, without further purification. It can be used in the next step. LRMS (m/z): 440 (M+l)+ c ) (5&gt;1 -(2-(6_fluoroimidazo[1,2_tf]pyridine_3_yl)) (8) Addition of 2M aqueous sodium hydroxide (4 μL, 〇73 mmol) to (6)-1-(2-) (6-fluoroimidazo[1,2 but pyridine-3-enyl-based: arylamino)pyrimidin-4-yl)pyrrolidine-2-carboxylic acid methyl ester (123 mg, 〇24 mol, preparation 82b) The mixture was obtained in a solution of methanol (5 ml) at room temperature overnight. Then solvent was evaporated and redissolved with water = 2 aqueous solution of hydrochloric acid was added until neutral, added, dried and dried to give 30 mg (25%) title ; White solid LRMS (m/z): 426 (M+l) + Preparation 83 W-2-(6-odor wow 叩 叩 小 小 ) ) _ _) amine

a)(8)-3-(2-(6-Fluorine_Salt)[6] -4-amino-based) Addition of H6-chloro-2-(6-fluoro·sodium(R)-pyrazine) mercaptoamine) piperidine-1-decanoic acid tert-butyl ester (132 mg, 〇30 mmol) To sodium sterol solution (from 5 mg (0.65 mmol) containing 丨 23 201130835

LRMS (m/z): 443 (M+l)+ b) (Λ)-2-(6·fluoroimidazolyl, 2峋pyridine_3•yl)6-indole-3-yl)pyrimidine _4_amine is slightly bitten by w_3_(2-(6-piper&lt;1,2-[alpha]pyridin-3-yl) each methoxypyrimidinyl) according to the procedure described in Preparation 74b Preparation of tert-butyl phthalate (117 mg, 0.26 mmol, Preparation 83a) and trifluoroacetic acid (102 μL, 1.32 mmol). The title compound (90 mg, 100%) was obtained as a white solid. , *, ",,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, + lH NMR δ (CDC13): 1.5-2.0 (m, 5H), 2.7-3 2 (m, 4H), 3.7 (bs, 1H), 4.0 (d, 3H), 5.2 (d, 1H), 5.6 ( s, 1H) η 2 (m 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.9 (dd, 1H) 〇' · Preparation 84 (J?)-2-(6-fluoroimidazo[ l,2-ii]pyridine-3_yl)_#·(bite_3_yl)-6-(2-(0-Butyl-1-yl)ethoxy)-bite-4*•amine

235 201130835 基)-6-Fluor a) 3·(4·Qixin (2-10 pirolidinyl)-ethoxy)pyrimidine 2 Iso-[1,2-ίΐ]ββ唆唆2-( Pyrrolidine small base) ethanol (186 μl, 丨59亳 莫加 to sodium hydride (64 mg 60% mineral oil suspension, 16 〇 mM, anhydrous tetrahydrogen (5 ml)) Compound for 30 minutes. Then add 3_(4, b dichloro to do 2_yl)_6- odor ^ [1, 2♦ than bite (3GG mg, L () 6 亳 Mo, preparation 72b) four cough = (10 ml) solution and the reaction mixture obtained at room temperature overnight. The solvent residue of Taifa solvent was partitioned between water and dioxane. The organic phase was separated and washed with water and brine, and passed through sulfur-dry red solvent. The crude product was purified by flash chromatography (dichloromethane to 9:1 hexanes) to give the title product as a pale yellow (tetra) (yield: m/z): 362 (M) +l)+ NMR δ (CDCl3): 1.8 (m, 4H), 2.6 (m, 4H), 2.9 (t, b) W-3-(2-(6-fluoroimidol[ι,2.β) 】n than bite ·3_base)_6_(2_(0-rho-1-yl) ethoxylated bite _4_ylamino) sent bite small butyrate formic acid ~ Ϊ according to preparation 7 as described in the procedure , consisting of 3_(4·chloro-o-( Scales _ ethoxy ethoxy)pyrimidin-2-yl)-6-fluoroimidazopyridine (3 〇〇 〇 = 83: 83 mmol, preparation 84a) and (external 3_amino-based-1·carboxylic acid Table 410曰@415mg, 2.07mmol) Μmethylpyrrolidone (4 house) I. 加热12G °C under microwave irradiation to heat the mixture! Hours. By 236 201130835 by flash chromatography (di-methane Purification of the crude product to 9:1 dichloromethane/methanol) followed by reverse phase chromatography (from waters c_18 ceria, water/1:1 acetonitrile-methanol as the dissolving agent [0.1%] Purification of the v/v decanoic acid buffer 〇% to 100%). The title compound was obtained as a white solid (m/z): 526 (M+l) + c) (and)- 2-(6-fluoroimidazo[1,2-n]pyridin-3-yl)piperidine-3-yl)·6·(2_(β-pyridyl) ethoxy)pyrimidine-4-amine According to the procedure described in the preparation of the servant, by w_3_(2_(6 odor [1, 2♦ than 唆-3_ yl] &lt;6_(2 七比洛的布基) ethoxy) mouth bite) (4) Small formic acid tert-butyl vinegar (10) mg, 0.30 mmol, ^ 84b) and trifluoroacetic acid (235 μL, 3 〇 5 mmol) as a white semi-solid title compound (111 G, fan), = further purification in the next step. "No, LRMS (m/z): 426 (M+l) + Preparation 85 =)-2-(6-fluoroimidazolyl (1,2_picidine)) 6_(2_(ethoxyl) )-7V-(piperidin-3-yl)pyrimidine_4-aminophylline)

237 201130835 琳琳基) Ethanol (73 μl, ο. 65 mmol) added to the sodium hydride (24 mg 60% mineral oil suspension, 〇 6 〇 millimolar) of four nitrogen = hexane (5 ml) suspension The resulting mixture was stirred in the solution for 1 minute at room temperature. Then add W-H6_gas·2_(6·Flumir·D, 2 Chongling 3 base) Fuding ice-based amine base) Qian·Ting Ding g|( 18() mg, g 4〇毫莫耳' Prepare 73) and win the resulting reaction mixture for 4 () hours under reflux. The solvent was evaporated and the residue was partitioned between water and water. Separation of the organic phase, water and fins, sulfur-filament and evaporation_. The crude product was purified by flash chromatography eluting elut elut elut elut elut elut LRMS (m/z): 542 (M+l) + lH NMR 6 (CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 4H), 2.6 (m, 4H), 2.8 (t, 2H) , 3.1-3.3 (m, 2H), 3.6 (m, 2H), 3.7 (ms 4H), 3.9 (m, 1H), 4.6 (t, 2H), 4.9 (s, 1H), 5.6 (s, 1H) 7 2 (m' 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.8 (dd, 1H) 〇( ? b)(8)-2·(6-fluoroimidol [nap pyridine] _6)_6-(2 for morpholinyl) ethoxy)-#-(Big -3-yl) gnace-4-amine according to the procedure described in Preparation 74b, by (and) _3_(2_( 6_Fluoroimidazo[1,2-small ratio bite_3_yl)-6-(2-(N-morphinyl)ethoxy)-penetrating _4_ylamino) piperidine-1·formic acid Third butyl ester (147 mg, 0.27 mmol, preparation 851) and trifluoroacetic acid (210 μl ' 2.73 mmol) were prepared by flash chromatography (dichloromethane to 85:15 dichloromethane) Purification of the crude product: mp. LRMS (m/z): 442 (M+l)+ 238 201130835 lU NMR δ (CDC13): 1.6-2.0 (m, 4H), 2.6 (m, 4H), 2.8-2.9 (m, 5H), 3.2 ( Dd, 1H), 3.6 (bs, 2H), 3.7 (m, 4H), 4.6 (t, 2H), 5.6 (s, 1H), 5.7 (bs, 1H), 7.2 (m, 1H), 7.7 (dd , 1H), 8.5 (s, 1H), 9.9 (dd, 1H). Preparation 86 (Λ)-2-(6-fluoroimidazo[1,2-«]»pyridin-3-yl)-6-(2-methoxyethoxy)-?V-(派 bit-3- Methyl hydrazine

a) 〇R)-3-(2-(6-fluoroimidazo[1,2_ίφ-pyridine-3-yl)-6-(2-methoxyethoxy)pyrimidin-4-ylamino)piperidine 1-butylic acid tert-butyl ester according to the procedure described in Preparation 85a, from (i?)-3-(6-Gas-2-(6-fluoroimidazo[1,2-β]pyridin-3-yl) Pyrimidin-4-ylamino)piperidine-1-decanoic acid tert-butyl ester (200 mg, 0.45 mmol, preparation 73), 2-methoxyethanol (170 μL, 2.23 mmol) and Prepared by sodium hydride (90 mg 60% mineral oil suspension, 2.23 mmol). Purification of crude by reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-nonanol as eliminator [0.1% ν/ν citric acid buffer] 0% to 100%) The product gave 63 mg (29%). LRMS (m/z): 487 (M+l) + lR NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 5H), 3.2 (m, 2H), 3.4 (s, 3H) , 3.6 (m, 1H), 3.8 (m, 2H), 3.9 (bs, 1H), 239 201130835 4.6 (m, 2H), 4.9 (bs, 1H), 5 7 1H), 8.5 (s, 1H), 9.8 (dd, 1H). ), 7.2 (m,1H)' 7.7 (dd, oxy)·((), mouth bite_4·amine 丞)H2-methoxyl B according to the procedure described in Preparation 74b, by [1] , 2♦ 岭3_基)_6_(2_?oxyethoxy oxime 气 唆 小 and small formic acid third butyl @ (63 mg, 毫 2 2 amino-based trifluoroacetic acid (50 μl, 0.65 毫Prepare 86a) and the age of the body λ 2 to prepare a W compound (5G money, / /) which can be used in the next step. 1 Progressive purification LRMS (m / z): 387 (M+l)+ Preparation 87 Fluorine shirt is called _·3·基)·6·(material·3_ylamino group)

a) (6) o-yl group -2 (6. fluoroimimadin oxime -4-ylamino) piperidine-1-carboxylic acid tert-butyl ester ^ dicyandi zinc (220 mg, 1.87 m Mohr) and bismuth phosphine) 〇 (〇) (286 mg, 0.25 mmol) added to (8)·3_(6-chloro;^fluoroimidazo[1,2]pyridin-3-yl)pyrimidine_4 _ ylamino) piperidine methadone dibutyl ester (1.1 g, 2.46 mmol, preparation 73) w, _ dimethyl carb 240 201130835 = amine (3 G ML) solution and under 13 在 in an argon atmosphere Chlorine: When. The solvent is then evaporated and the residue is partitioned between water and dryness. The organic phase is separated from the organic phase, washed with water and brine, and dried over sulphuric acid and red solvent. by flash chromatography (dichloromethyl to 95:5 / methanol) The crude product was purified to give the title product as i <RTI ID=0.0>===================================================== 2.0 (m, 4Η), 口-4.3 (m, 5H), 5.3 (s, ih), 5.5 (bs, 1H), 6 5 (s ih) 7 3 r out), 7.7 (dd, 1H), 8.6 (s, iH). (s, 1H), 7.3 (m, basal, 2. -3-yl)-6-age 3-amine according to the procedure described in Preparation 74b, And [ι, 2♦ than bite · base) money - 4 · Α (on your cyano · 2 · (6_ fluorobut # 胺 amino) piperidine -1 - formic acid third = (1 〇〇 mg, 0.23 mmol, Preparation 87a) Microliter '1.44 mmol" was prepared. Obtained a chaotic B: (4) g '%), which was purified without further purification LRMS (m/z): 338 (M+l )+

^HNMRS •1 (bs, 1H), 6.1 (bs, 1H), 6.5 (s, im (ton 8.5 (S,1H), 9.8 (dd,m) /,1H),7 3 plus,1H),7.7 (dd, preparation of 88 W-scented saliva and U, 2 bite I base called (Brigade bite each 241 201130835 base)_6_(2 from tetrazole-s-yl)pyrimidine 4 amine

Azido dimethyltin (38 mg, 〇18 mmol (8)_3-(6-cyano·2_(6-fluorinated fluorene, 2--3-yl=yl) fluorene f_1_carboxylic acid Triterpene (5 mg, 0.11 mmol, preparation 8'7a) in a solution (2 ml) / broth and the mixture was heated to reflux for 4 hours. The solvent was evaporated and the residue was evaporated. It was suspended in diethyl ether and stirred overnight. The resulting pale yellow solid was filtered and dried to give 5 mg (yield: 94%) of title product. LRMS (m/z): 481 (M+l) + , Η ΝΜ^ δ ( (CD, 13H) , 7.3 (m, 2H), 7.7 (dd, 1H), 8.6 (s, 1H), 10.1 (d, 1H). ' ' b ) (and) -2- (6- oxazolo[1,2- Fl]pyridin-3-yl (bunker ·3_yl)-6-(2/Γ-tetra, sal _5_yl) shouting bite 4-amine, according to the procedure described in Preparation 74b, from (8)-3 -(2_(6_fluoroimidazo[1,2·α]acridine I-based tetras--5-yl)pyrimidin-4-ylamino)pyridinium + tert-butyl formate (2 mg, 0.42 Millol, preparation 88a) and three 242 201130835 fluoroacetic acid (160 microliters, 2.08 millimoles) Obtained 54 mg (54%) of the title compound m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m -fluoroimidazo[l,2_fl]acridin-3-yl)-6-(1-methyl-LfiT-tetrazol-5-yl)pyrimidin-4-ylamino)piperidine-1-carboxylic acid Butyl ester and (i?)-3-(2-(6-fluoroimidazo[l,2_fl] «pyridin-3-yl)-6-(2-mercapto-2 ugly-tetrazol-5-yl Pyrimidin-4-ylamino)piperidine-1-carboxylic acid tert-butyl ester

Potassium carbonate (190 mg, 1.35 mmol) and iodonane (84 μL, 1.35 mmol) were added to (Magic-3-(6-fluoroimidazo[1,2-α]吼) Bite-3-yl)-6-(2//-four° sit-5-yl) Mouthlide-4-ylamino) 唆-1-carboxylic acid second butyl ester (590 mg, 1.23 mmol, Prepare a solution of the dimethylformamide (5 ml) of 88a) and stir the reaction mixture at room temperature for 2 hours, then pour in 20 ml of water. The resulting pale yellow solid was filtered, washed with water and dried. The crude isomer mixture was purified by chromatography (dioxane to 94:6 hexanes / methanol) to afford 98. And 125 mg (21%) of the major isomer as a solid (second peak of dissolution). Minor isomer: 243 201130835 LRMS (m/z): 495 (M+l) + ]H NMR δ ( CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 5H), 3.4-3.6 (m, 3H), 3.8 (d, 1H), 4.6 (s, 3H), 5.7 (bs, 1H), 7.3 (m, 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.8 (dd, 1H). Main isomer: LRMS (m/z): 495 (M+l) + ] NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.1 (m, 5H), 3.5 (m, 3H), 3.8 (d, 1H), 4.5 (s, 3H), 5.3 (bs, 1H), 7.1 (s, 1H), 7.3 (m, 1H), 7.7 ( Dd,1H), 8.6 (s,1H),10.1 (dd,1H). Preparation 90 (/0-2-(6-fluoroimidazo[1,2-ίΐ] acridine-3-yl)-6- (1-methyl-1opentetrazol-5-yl)-indole "-(piperidin-3-yl)pyrimidine-4-amine

According to the procedure described in Preparation 74b, (i?)-3-(2-(6-fluoroimidazo[1,2-α]σ ratio -3-yl)-6-(1-indolyl- 1//·四0坐-5-yl) Cyclohexyl-4-ylamino) Piperidine-1-decanoic acid tert-butyl ester (98 mg, 0.20 mmol), minor isomerism from Preparation 89 Preparation) and trifluoroacetic acid (152 μl, 1.97 mmol). 48 mg (61%) of the title compound was obtained and used in the next step without further purification. LRMS (m/z): 395 (M+l)+ 244 201130835 NMR δ (CDC13): 1.6-2.0 (m, 5H), 2.9 (m, 3H), 3.2 (dd, 1H), 4.3 (bs, 1H ), 4.6 (s, 3H), 6.0 (bs, 1H), 7.2 (s, 1H), 7.3 (m, 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.8 (dd, 1H) . Preparation 91 (1?)·2·(6_fluoroimidazo[1,2-&lt;|]pyridine-3-yl)-6-(2-methyl-2 ugly-tetrazol-5-yl)- Λ"-(piperidin-3-yl)pyrimidine-4-amine

According to the procedure described in Preparation 74b, from (Λ)-3-(2-(6-fluoroimidazo[1π-predative-3-yl)-6-(2-indolyl-2//. -5·yl)m-butyl-4-ylamino) piperidine-1-decanoic acid tert-butyl ester (125 mg, 0.25 mmol, from the major isomer of Preparation 89) and trifluoroacetic acid (195 Microliter, 2.53 millimoles) Preparation. 40 mg (40%) of the title compound was obtained and used in the next step without further purification. LRMS (m/z): 395 (M+l)+ !H NMR δ (CDC13): 1.6-2.0 (m, 5H), 2.8-2.9 (m, 3H); 3.2 (dd, 1H), 4.5 (s , 3H), 5.7 (bs, 1H), 7.1_ (s, 1H), 7.3 (m, 1H), 7.7 (dd, 1H), 8.6 (s, 1H), 10.1 (dd, 1H). Preparation 92 (i〇-2-(6-fluoroimidazo[l,2_ii]acridin-3-yl)-6-(piperidin-3-ylamino)pyrimidine-4-carboxylic acid 245 201130835

Anthraquinone (Third Butoxyxyl) brigade bite _3_ylamino)_2_(6_ odor and [1,2·ίΐ] ° pyridine·3·yl)pyrimidine _4 formic acid to =m (4.5 ml, 36 mmol) added = spectrum cyano fluorocarbon 卯, 2_3_ base) money _4 base, base 卞 卞 formic acid third vinegar (45. mg, 1 () 3 mM, prepared In a solution of methanol (8 ml) and under the microwave irradiation, the compound was added for 1 hour. Then the reaction mixture was diluted with a gas and washed with a gas-like solution, and then acidified until it was white. Solid (male). The product was extracted with a water-purified product and dried with water. The solvent was evaporated and evaporated to give 247 mg (53%) of white product as a white solid. LRMS (m/z): 457 (M +l)+b)(i?)-2-(6-azamidazolium with a small pyridine-3-yl group)_6_(Nantidine-3-ylamino)pyrimidine-4·carboxylic acid as described in Preparation 74b Procedure: Preparation of 92a from (t-butoxycarbonyl) piperidin-3-ylamino)-}(6-fluoroimidazolyl &lt;RTIgt;]pyridyl)pyrimidin-4-4 carboxylic acid (247 mg, 0.54 mmol) And trifluoroacetic acid (21 〇 microliter, 2.73 mmol) to obtain 167 mg (87%) of the title compound The residue was used in the next step without further purification. LRMS (m/z): 357 (M+l) + 201130835 Preparation 93 (i〇-2-(6-fluoroimidazo[1,2-ύί]pyridine-3 -yl)-TV4-(piperidin-3-yl)pyrimidine-4,6-diamine

a) 〇R)_3-(2-(6-fluoroimidazo[l,2-ii]-lapropion-3-yl)-6-(4-methoxybenzylamino)pyrimidin-4-ylamine Benzylpyridine-1-carboxylic acid tert-butyl ester according to the procedure described in Preparation 76a, from (i?)-3-(6-chloro-2-(6-fluoroimidazo[1,2"]pyridine- 3-butyl)pyrimidin-4-ylamino)piperidine-1-decanoic acid tert-butyl ester (245 mg, 0.55 mmol, preparation 73) and (4-methoxyphenyl) decylamine (376 mg) , 2.74 millimolar) preparation. The crude product was purified by flash chromatography eluting elut elut elut elut elut LRMS (m/z): 548 (M+l)+]H NMR δ (CDC13): 1.4 (s, 9H), 1.6-2.0 (m, 3H), 3.2 (bs, 2H), 3.6 (m, 3H) ), 3.8 (s, 3H), 4.5 (d, 2H), 4.7 (d, 1H), 5.1 (bs, 1H), 5.3 (bs, 1H), 6.9 (d, 2H), 7.2 (m, 1H) , 7.3 (d, 2H), 7.6_(dd, 1H), 8.5 (s, 1H), 9.9 (dd, 1H). .- b)(i?)_2-(6-fluoroimidazo[1,2-fl]pyridin-3-yl HV4·(piperidin-3-yl)pyrimidine-4,6-diamine (255 μl, 3.32 mmol) added to (i?)-3-(2-(6- 247 201130835 scented saliva [I, 2 rushed to bite _3·yl) _6_(4) methoxy benzylamine Base) ♦ _4_ 胺 ) ) 钱 小 小 小 第三 181 181 181 181 181 181 181 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( After 64 hours and under the thief _ mix 2G hours. Then the solvent was treated with saturated aqueous sodium hydrogencarbonate solution. The aqueous solution was extracted with water and the water layer was washed with water and brine. __ 生 108 mg (brain) was pale yellow solid Title: LRMS (m/z): 328 (M+l) + lH NMR 6 (C〇Cl3): 〇(m, 3H), 2.6-2.9 (m, 祀), 3.2 (dd, 1H), 4.6 (bs, 2H), w (d, m), 5 2 (m, 1H), 7.6 (dd, 1H), 8.5 (s, 1H), lo.o (10), 1H) Prepare 94, 3-( 4'6-digas-5-fluoro is more than 2-yl)_6_fluoromime

a) 5-Fluoro-2-(6-fluoro-dosing [1,2_φ-pyridyl-3-ylpyridyl-4 6 diol according to the procedure described in Preparation 72a, from 6-fluoroimidazolium]]pyridine 3-Carboxylium carbamide (2.00 g, 8.39 mmol, Preparation 42b) and 2-fluoromalonic acid diethyl acetonate (2.65 mL, 16 8 mmol). Separated 0.95 g (43%) The title product is a white solid. LRMS (m/z): 265 (M+l) + 248 201130835 4 NMR δ (DMSO-^): 7.6 (s, 1H), 7.8 (s, 1H), 8.7 ( s, 1H), 10.1 (s, 1H), 12.6 (bs, 1H) 〇b) 3-(4,6·two gas _5_Fluor shouting base) Winter fluprom and m small bite according to preparation 72b The procedure described in the procedure, consisting of 5-fluoro-2-(6-fluoroimidazo[1,2-oxime--3-yl)-biting-4,6-diol (0.95 g, 3.60 mmol) Preparation of the ear, Preparation 94a) and phosphorus oxychloride (7.35 mL). The title compound (0.71 g, 63%) eluted LRMS (m/z): 302 (M+l)+ Preparation 95 (Λ)-5-fluoro-2-(6-fluoroimidazo[1,2-&lt;|]"pyridin-3-yl)- 6_(N_Merynyl)-Λ"-(piperidin-3-yl)pyrimidine-4-amine

a) (and gas winter fluoride-2·(6-fluoroimidol[l,2-a]〇it -3-yl) 嚷-4-ylamino)piperidine·carboxylic acid tert-butyl ester according to The procedure described in Preparation 73, from 3-(4,6·dioxa-5-fluoropyrimidin-2-ylfluoroimidazo[1,2-α]pyridine (420 mg, 1.39 mmol, Preparation 94b) And (8) 3-3-aminopiperidine-1-decanoic acid tert-butyl ester (56 mg, 2.79 mmol) prepared by flash chromatography (di-methane to 95:5 dichloromethane / methanol) The crude product was purified to give the title compound (md: sd, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, ), 5.4 (bs melon 1H), 7.7 (dd, 1H), 8.5 (s, 1H), 9.7 (dd, 1H), , (, b) W-3-(5-fluoro-2-(6-) Fluorine-salt and [u-external 唆3-based)_6_(n_Mallinyl) gnace-4-ylamino) brigade formic acid tributyl hydrazine t according to: Preparation 76a * described procedure, by; '(6 _Chlorine_5_Fluorine fluoride and [U-唆唆_3_基) money_4 Small formic acid second purpose (10) mg, 〇.41 millimolar (10) ^ Strong mouth mixture for 2 hours. Get = 〇 milli ^ (66/.) title compound and can be used in the next step LRMS (m/z) without further purification : 516 (M+l)+ 】HNMR δ (CDCl3): M (s,9H),1.6].9 (m,5H), 3.5 (m 1H), 7.7 (dd,1H), 8.4 (s, 1H), 9 8 (10) c) WS-Fluoro-2-(6-fluoro-salt and called Xiaoling Lumline)--(Big -3-K) screams bite amine, as described in Preparation 74b Procedure, by (i〇-3m(6_fluoroisoxazole[1,2 rushing 3·yl)_6,?# _ formic acid third butyl from the purpose (14G milliliter, n97 丄 money base) (iv) trifluoroacetic acid (9) Microliter, 〇.65 mmol 2): Preparation of 95b) and pen bucket). Obtained 8 〇 $ $ f 71%) title compound in solid form and did not advance - step pure - step 250 201130835

LRMS (m/z): 416 (M+l) + Preparation 96 6-Fluoro-3-(4-fluoro-6-decyloxy-5-(trifluoromethyl)pyrimidin-2-yl)imidazo[ 1,2-ίΐ]11 than bite

F

ΝΗ

Add water (8 ml) and ι, 3,3,3-tetrafluoro·丨_曱oxy_2·(trifluoromethyl)propan-1·ene (670 μl, 7·08 mmol) To a 6-fluoroimidazole and a mixture of 2-3-1 hydrazine amine (1.52 g, 4.76 mmol, preparation 42b) in dioxane (10 ml). The reaction mixture was cooled in an ice-bath and aqueous EtOAc (2 mL, Stir at ambient temperature for 3 hours. Dilute the mixture with an excess of two gas. The organic layer was separated and washed with EtOAc EtOAc (EtOAc m. /z): 331 (M+l)+ ; lower-step. Preparation 97 (J?)-2-(6-fluoroimidazolium acridine-3-yl)·6-pyridine-3-yl)-5-(trifluoromethyl)-pyro- 4-aminooxy (Brigade 251 201130835

#)-3-(6-fluoroimidazolium _u_e]pyridine·3yl)6-methoxy-5-(trifluoromethyl)pyrimidin-4-ylamino)piperidinecarboxylic acid tert-butyl Ester,)-3-Amine travel brigade ·!·Formic acid third butyl 酉 ('muck gram, 143 added to 6|3_(4_ gas_6_methoxy ketone (tri-methyl thiol) The mixture was mixed with a bite (236 mg, 〇71 mmol, preparation 96) ^ ethanol, (5 ml) solution and the mixture was allowed to stand at room temperature for 3 hours. The solvent was evaporated and the residue was purified EtOAcjjjjjjjjjjjj Compound LRMS (m/z): 511 (M+l) + b) (and)-2-(6-fluoroimidazo[l,2-n]pyridine-3-yl)-6-methoxy- Λ4pyridinyl)-5-(trifluoromethyl)acridin-4-amine according to the procedure described in Preparation 74b, from (7))_3_(2_(6-fluoroimidazo[1,2-punching ratio bite- 3-yl)-6-decyloxy-5-(trimethylmethyl)pyrimidine-4-aminoamine) Bite 1-carboxylic acid tert-butyl ester (106 mg, (U1 millimolar, preparation 9) ^a) and trifluoroacetic acid (80 μl '1·04_ The title compound was obtained as a white solid. mp (m/z): 411 (M+l) + NMR δ (CDC13): 1.6-2.0 (m, 5H) ), 2.8-2 9 (m 3H), 3.2 (dd, 1H), 4.1 (s, 3H), 4.3 (m, 1H), 6.2 (bs, 1H), 7; 252 201130835 (m, 1H), 7.7 (dd, 1H), 8.6 (s, 1H), 9.8 (dd, 1H) 〇Example 1 3·(Μ_)-ΐ-phenethyl]amino}pyrimidine I group) Isozoline u, pyridine-6- Nitrile

According to the experimental procedure as described in Preparation 5a 'by 3_(4_ via base biting... soil) imidazo[l,2-a]pyridine_6-carbonitrile (preparation 牝, 〇m gram, 〇74 mM Ear) and (Xi-1_phenyl-ethylamine (〇48 ml, 3 68 mmol) obtained a yellow solid (0.102 g, 40%). The solvent was removed in vacuo and by reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 B guess • methanol as a dissolving agent [0.1% v/v citric acid buffer] 〇% to 1%) Purification residue 'produces a yellow solid The title compound (〇102 g, 40%) 〇LRMS (m/z): 341 (M+l)+. iH-NMR δ (DMSO-): 1.53 (d, 3H), 5.28 (bs, 1H) ), 6.52 (bs, 1H), 7.22 (d, 1H), 7.36 (d, 2H), 7.48 (d, 2H), 7.67 (d, 1H), 7.87 (d, 1H), 8.19 (d, 1H) , 8.26 (bs, 1H), 8.42 (bs, 1H), 10.27 (bs, 1H). 'Example 2 3-(4-{[(1Λ)-1-phenethyl)amino}pyrimidin-2-yl Imidazole ratio 253 201130835 pyridine-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]acridin-6-carbonitrile (Preparation 4b) and phenyl-ethylamine Obtained as a white solid (70%). After completion of the reaction, the mixture was partitioned between water and dichloromethane. The organic layer was washed with EtOAcqqqqqqqqm LRMS (m/z): 341 (M+l)+. ^-NMR δ (DMSO-4): 1.52 (d, 3H), 5.30 (bs, 1H), 6.52 (d, 1H), 7.22 (d, 1H), 7.34 (t, 2H), 7.48 (d, 2H) ), 7.68 (d, 1H), 7.88 (d, 1H), 8.19 (d, 1H), 8.24 (d, 1H), 8.43 (s, 1H), 10.28 (bs, 1H) Example 3 3_[4-( Benzylamino)pyrimidin-2-yl]imidazo[1,2-d]acridine-6-carbonitrile

254 201130835 according to the experimental procedure as described in Preparation 5a 'from 3_(4-hydroxypyrimidin-2-yl)imiindole[l,2-a]pyridine-6-indenecarbonitrile (Preparation 4b) and phenylmethylamine A yellow solid (60%) was obtained. By reverse phase chromatography (C-18 from Waters), -18 acetonitrile-sterol, as a dissolving agent [via 〇.1〇/0 v/v citrate buffer] 0% to After purifying the crude reaction with 100%), the desired compound is obtained. LRMS (m/z): 327 (M+l)+. W-NMR δ (DMSO〇: 5.76 (bs, 2H), 6.61 (bs, 1H), 7.25 - 7.4 (m, 5H), 7.68 (d, 1H), 7.89 (d, 1H), 8.17 - 8.36 (m , 2H), 8.48 (s, 1H), 10.37 (bs, 1H) Example 4 3-(4-{[(lS)-2-methoxy-1-methylethyl]amino}pyrimidin-2- Isozo[1,2-&lt;ι]pyridine-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[l,2-a]pyridine each nitrileonitrile (Preparation 4b) and (6) Phenoxypropanol The amine gave a white solid (33 〇 / 〇). After completion of the reaction, the mixture was partitioned between water and dichloromethane. The organic layer was washed with water, brine, dried (M.sub.4) and evaporated. The residue was purified by flash chromatography (98:2 to 96:4 hexanes / 255 201130835 sterol). LRMS (m/z): 307 (M-l)+. ^-NMR δ (CDC13): 1.36 (d, 3H), 3.43 (s, 3H), 4.27 (bs, 1H), 5.25 (bs, 1H), 6.26 (d, 1H), 7.40 (d, 1H) 7 1H) 8.24 8.58 10.56 (s,lH) Example 5 3-{4-[(cyclohexylmethyl)amino]pyrimidine_2_yl}isoxolopyridine-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, 3_(4-hydroxypyrimidin-2-ylcarbazol [1,2 pyridine/6-indolecarbonitrile (preparation 4b) and cyclohexylmethylamine) was obtained. White © (50%) After completion of the reaction, the mixture was partitioned between water and methane. The organic layer was washed with water and then extracted with aqueous 2H hydrochloric acid. The aqueous phase was basified with 6 M aqueous sodium hydroxide, and then The oil was extracted and dried. The organic layer was dried (MgSO4) and evaporated to give the title compound. NMR (m/z): 333 (M+l) + h-NMR δ (CDCl3): 0.91 - 03 (m, letter) , i _ 2 〇5 (m, 1H), 3.13 - 3.33 (bs, 1H), 3.40 (d, 2H)&gt; 6.24 (d, 1H), 7.4〇(d,1H), 7.78 (d,1H) , 8.18 - 8.36 (m, iH), 8 59 (b 10.56 (bs, lH)., m), 256 201130835 Example 6 3-{4-[(2-Methoxyethyl)amino]pyrimidine-2- Base imidazo[1,2-&lt;φ ratio pyridine-6-method

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]pyridin-6-indolecarbonitrile (Preparation 4b) and 2-methoxyl The amine gave a white solid (60%). LRMS (m/z): 295 (M+l)+. ^-NMR δ (DMSO-J6): 3.08 - 3.76 (m, 4H), 3.36 (s, 3H), 6.50 (d, 1H), 7.73 (d, 1H), 7.84 (bs, 1H), 7.94 (d , 1H), 8.23 (bs, 1H), 8.52 (s, 1H), 10.52 (bs, 1H) Example 7 3-{4-[(l-adamantyl)amino]pyrimidin-2-yl} Imidazo[1,2-ii] 0 ratio bite-6-a guess

257 201130835 According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[l,2-a]pyridine-6-indolecarbonitrile (Preparation 4b) and 1-(1) -Adamantyl)methylamine gave a white solid (51%). The crude product was purified by flash chromatography (100:8:1 dioxane / methanol / aqueous ammonia). LRMS (m/z): 385 (M+l)+. 'H-NMR δ (DMSO-i/6): 1·6〇- 1.66 (m, 12H), 1.86 -2.03 (m, 3H), 4.67 (s, 2H), 6.48 (d, 1H), 7.64 ( Bs, 1H), 7.68 (d, 1H), 7.89 (d, 1H), 8.13 (d, 1H), 8.48 (bs, H) 10.56 (bs, 1H). Example 8 3-{4-[(2,2-Dimethylpropyl)amino]pyrimidin-2-yl}imidazo[1,2_«]"pyridin-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]pyridin-6-indolecarbonitrile (Preparation 4b) and 2,2-diindole The propyl-1-amine gave a white solid (26%). Purification of crude by reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-nonanol as eliminator [0.1% v/v citric acid buffer] 0% to 100%) product. LRMS (m/z): 307 (M+l)+. H-NMR δ (DMSO-i/6): 1·〇3 (s, 9H), 4.17 (d, 2H), 6.54 258 201130835 (d,1H), 7.64 - 7.73 (bs,1H),7.72 ( d, 1H), 7.95 (d, 1H), 8.19 (d, 1H), 8.53 (s, 1H), 10.59 (bs, 1H). Example 2 3-{5-Bromo-4-[(2,2-dipropylpropyl)amino]pyrimidin-2-yl}imidazopyridin-6-carbonitrile

To the stirred 3-{4-[(2,2·dipropylpropyl)amino]pyrimidin-2-ylbomizole[1,2-0]pyridine each carbonitrile (Example 8, 0.300 g, Potassium acetate (〇.1〇4 g, 1 j mmol) was added to a solution of acetic acid (3.6 ml). The mixture was cooled (ice bath) and a solution of bromo (0.050 mL, EtOAc) (EtOAc) The reaction was then stirred at ambient temperature for 1 hour. A saturated aqueous solution of sodium carbonate (30 ml) was added and mixture was extracted with ethyl acetate. The organic layer was washed with EtOAc (EtOAc m. H-NMR δ (CDC13): 1.06 (s, 9H), 3.49 (d, 2H), 5.62 (bt, 1H), 7.42 (ddd, 1H), 7.80 (ddd, 2H), 8.37 (d, lH) , 8.60 (d, 1H), 10.48 (m, 1H) 259 201130835 Example ίο 3-{4_[(2,2·Dimethylpropyl)amino]-5-piperazin-1-ylpyrimidin-2-yl }Mi Jun and [l,2_a]D than bite-6-carbonitrile

a) bubbling nitrogen through the 3-{5-bromo-4-[(2,2-dimercaptopropyl)amino]-containing sigma-but-2-yl} sigma contained in the microwave reaction vessel and [ 1,2-fl]0 than bite-6-carbonitrile (Example 9, 0.105 g, 0.27 mmol), piperazine-1-carboxylic acid tert-butyl ester (0.152 g, 0.82 mmol), third A mixture of sodium alkoxide (0.079 g, 0.82 mmol) and biphenyl-2-yl-di-tert-butylphosphine (0.020 g, 0.07 mmol) in toluene (2.5 mL) was applied for 5 min. Next, ginseng (diphenylfluorenylacetone) dipalladium (0) (0.125 g, 0.14 mmol) was added, and the vessel was sealed and subjected to microwave irradiation at 115 ° C for 1 hour. Water and ethyl acetate were added to the mixture, and the organic layer was dried (MgSO4) and evaporated. Purification of the residue by reverse phase chromatography (C-18 from Waters, water/1:1 acetonitrile-methanol as the eluent [0.1% v/v formic acid buffer] 0% to 100%) , resulting in a yellow solid 4~{2-(6-cyanoimidazo[1,2-α]acridin-3-yl)-4-[(2,2-dipropylpropyl)amino] Pyrimidin-5-yl} piperazine-1-carboxylic acid tert-butyl ester (0.023 g, 16%). LRMS (m/z): 491 (M+l)+. 260 201130835 ^-NMR δ (CDC13): 1.05 (s, 9H), 1.52 (d, 9H), 2.18 (d, 2H), 3.00 - 2.86 (m, 4H), 3.53 - 3.39 (m, 4H), 7.38 (d, 1H), 7.77 (d, 1H), 8.00 (s, 1H), 8.55 (s, 1H), 10.60 (s, 1H). b) to 4-{2-(6-cyanoimidazo[1,2-α]acridin-3-yl)-4-[(2,2-dimercaptopropyl)amino]pyrimidine-5- A solution of 4 hydrazine hydrochloride in 1,4-dioxane (0.140 mL, 0.56) was added to a solution of tert-butyl piperazine-1-decanoate (0.022 g, 0.04 mmol) in dioxane (1 mL). Millions of ears). The mixture was stirred at ambient temperature for 20 hours, then the solvent was evaporated and water was added. The aqueous layer was washed with dichloromethane, then basified with concentrated aqueous ammonia and extracted with dichloromethane. The title compound was obtained as a pale yellow solid. LRMS (m/z): 391 (M+l)+. ^-NMR δ (CDC13): 1.06 (s, 9H), 3.13 - 2.90 (m, 8H), 3.46 - 3.40 (m, 2H), 5.91 (t, 1H), 7.40 - 7.35 (m, 1H), 7.77 (d, 1H), 8.02 (s, 1H), 8.54 (s, 1H), 10.61 (s, m). Example 11 3-[4·[(2,2·Dimethylpropyl)amino]-5-(2-methoxyacridin-4-yl)pyrimidin-2-yl]imidazo[1,2- a] acridine-6-carbonitrile

261 201130835 According to the experimental procedure as described in Preparation 27d, from 3-{5-bromo-4-[(2,2-dipropylpropyl)amino]pyrimidin-2-yl}imidazo[1,2- α]pyridine-6-carbonitrile (Example 9) and 2-decyloxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboryl)pyridine (preparation 38) ) Obtained as a pale yellow solid (54%). The crude product mixture was filtered through Celite® and the filter cake was washed with ethyl acetate. The solvent was removed under reduced pressure and subjected to reverse phase chromatography (from Waters C-18 cerium oxide, water/1:1 acetonitrile-nonanol as the eliminating agent [passed with 0.1% v/v citric acid] The residue is purified from 0% to 100% to give the desired compound. LRMS (m/z): 414 (M+l)+. !H-NMR δ (CDC13): 1.03 (s, 9H), 3.47 (bs, 2H), 4.04 (s, 3H), 5.31 (d, 1H), 6.86 (s, 1H), 6.99 (t, 1H) , 7.44 (d, 1H), 7.82 (d, 1H), 8.18 (s, 1H), 8.34 (t, 1H), 8.67 (s, 1H), 10.62 (s, 1H). Example 12 3-[4-[(2,2-Dimethylpropyl)amino]-5-(2-o-oxy-1,2-dihydroacridin-4-yl) Mouth-2-yl ]啼峻和[1,2-3]0 than bite-6-a guess

According to the experimental procedure as described in Preparation 4b, 3-[4-[(2,2-dimercaptopropyl)amino]-5-(2-indolyl)-bito-indole-based cancer Ding-2-yl] sigma beta sits and [1,2-β] 262 201130835 Pyridine-6-carbonitrile (Example 11) gave a solid (63%). LRMS (m/z): 400 (M+l)+. !H-NMR δ (DMSO-4): 1.05 (s, 9H), 3.47 (d, 2H), 6 34 (d, 1H), 6.53 (s, 1H), 7.45 (bs, 1H), 7.60 (d , 1H), 7.87 (d 1H), 8.05 (d, 1H), 8.28 (s, 1H), 8.72 (s, 1H), 10.54 (s, 1H). 'Example 13 3-{4-[(2,2-Dimethylpropyl)amino]-5-pyridin-3-ylpyrimidin-2-yl} taste seat and [l,2-a]0 bite- 6-carbonitrile

According to the experimental procedure as described in Preparation 5a 'from 3-(4-carbazyl-5-pyridin-3-ylpyrimidin-2-yl)isoxazo[l,2-fl]pyridine-6-carbonitrile (Preparation 26b) and neopentylamine afforded a yellow solid (22%), followed by reverse phase chromatography (from Waters C-18 cerium oxide, water/1:1 acetonitrile-methanol as the eliminator) % v/v citric acid buffer] 0% to 100%) The crude product was purified. , LRMS (m/z): 384 (M+l)+. ^-NMR δ (CDC13): LOO (s, 9H)5 3.47 (d, 2H), 5 l〇(t 1H), 7.43 (ddd, 1H), 7.51 (dd, 2H), 7.81 (ddd, '2H ) '8 l5 (d 1H), 8.66 (s, 1H), 8.78 - 8.71 (m, 2H), 1〇·63 (dd m) ' Example 14 , 3-{4-[(3-Phenylphenyl) Amino group] money_2_base} smell sniffing [U a] bite 263 201130835 -6-A guess

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[l,2-a]acridin-6-indolecarbonitrile (Preparation 4b) and (3-fluorobenzene) The guanamine obtained a white solid (17%), followed by reverse phase chromatography (from Waters C-18 cerium oxide, water/1:1 acetonitrile-methanol as the eliminating agent [via 0.1% v/v The crude product was purified by citric acid buffer] 0% to 100%). LRMS (m/z): 345 (M+l)+. ^-NMR δ (DMSO-J6): 5.02 (bs, 2H), 6.64 - 6.97 (m, 1H), 7.29 - 7.46 (m, 1H), 7.59 (bs, 2H), 7.64 - 7.81 (m, 1H) , 7.87 - 8.07 (m, 1H), 8.10 - 8.35 (m, 1H), 8.57 (m, 2H), 8.79 (bs, 1H), 10.66 (bs, 1H) Example 15 3-{4-[(4- Fluorobenzyl)amino]pyrimidin-2-yl}imidazo[l,2-flp to pyridine-6-method

264 201130835 according to the experimental procedure as described in Preparation 5a by 3-(4-hydroxypyrimidin-2-yl) σm0 sitting and [1,2-&amp;]° ratio biting -6-indene nitrile (preparation servant) and 4· ι 基) methylamine obtained a white solid (11%), followed by reverse phase chromatography (from Waters C-18 cerium dioxide 'water / 1:1 acetonitrile - methanol as a leaching agent [丨% ν/ν Formic acid buffer] 0% to 1 〇〇〇 / 0) Purified crude product. LRMS (m/z): 345 (M+l)+. !H-NMR δ (CDC13): 4.65 (bs, 2H), 6.28 (d, 1H), 6.95 -7.13 (m, 2H), 7.26 (s, 1H), 7.31 - 7.45 (m, 2H), 7.77 ( d, 1H), 8.29 (d, 1H), 8.59 (s, 1H), 10.49 (bs, 1H) Example 16 3-{4-[(2-methylbenzyl)amino]pyrimidin-2-yl }Imidazo[1,2-micropyridin-6-carbonitrile

Obtained according to the experimental procedure described in Preparation 5a 'by the base of the thiophene-2-yl) imidazo[i,2-a]D-pyridyl-6-carbonitrile (preparative servant) and o-quinone methylamine White solid (39%) 'Water was then added and extracted with ethyl acetate. The organic layer was washed with water and brine <RTI ID=0.0>(~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ . 265 201130835 LRMS (m/z): 341 (M+l)+. H-NMR δ (DMSO-禹): 2.43 (m, 3H), 4 52 _ 4 85 (m, 2H), 6.38 6.73 (m, 1H), 7·10 - 7.30 (m, 3H), 7 3〇 _ 7 44 (m, 1H), 7.6G - 7.82 (m, 1H), 7.91 · 7.94 (m, 1H), 8 〇 4 _ 8 20 (m, 1H), 8.20 _ 8.36 (m, 1H), 8.43 - 8.61 (m, ih), 10.40 (bs, 1H). Example 17 2-({[2-(6-Cyano-sodium)-[l,2--bite- 3-yl) bite_4yl]amino}methyl)piperidine-1-carboxylic acid tert-butyl ester

Know: according to the experimental procedure described in Preparation 5a, from 3_(4_ via the base σ 定 基 基 基 峻 并 l [l, 2-a] pyridine-6-indene nitrile (preparation servant) and 2_ (Aminomercapto)piperidine-1-carboxylic acid tert-butyl ester (prepared as described in C/zem household/2 still 7/2 5w//, 1998, 787-796) gave a yellow solid (93%). Water was then added and extracted with EtOAc. EtOAc (EtOAc m. Compound LRMS (m/z): 434 (M+l)+.]H-NMR δ (CDC13): 1.46 (s, 9H), 1.55 - 1.86 (m, 4H), 2.80 - 2.97 (m, 1H) , 3.10 - 3.25 (m, 1H), 3.44 - 3.59 (m, 1H), 266 201130835 3.76 - 4.15 (m, 2H), 4.30 - 4.51 (m, 1H), 4.49 - 4.72 (m, 1H), 6.24 ( Bs, 1H), 7.42 (d, 1H), 7.78 (d, 1H), 8.22 (bs, 1H), 8.59 (s, 1H), 10.58 (bs, 1H) Example 3-(M[(l- 醯) Isopiperidin-2-yl)methyl]amino}pyrimidin-2-yl)carbazolo[1,2-&lt;1]° ratio bite_6_carbonitrile

a) according to the experimental procedure as described in Preparation 5b, from 2-({[2-(6· cyanosino[1,2-α]pyridin-3-yl)piperidin-4-yl]amine Benzyl) piperidine carboxylic acid tert-butyl ester (Example 17, 0.213 g, 0.49 mmol) afforded 3-{4-[(piperidin-2-ylmethyl)amino) as a white solid. Pyrimidin-2-yl}imidazo[1,2-α]πpyridin-6-carbonitrile (0.130 g, 80%). After the reaction was completed, water was added, followed by neutralizing the mixture with solid sodium hydrogencarbonate. The resulting precipitate was filtered, washed with water and dried in vacuo. LRMS (m/z): 334 (M+l)+. W-NMR δ (DMSCW6): 1·37 - ΐ·62 (m, 4Η), 1.65 - 1.85 (m, 2H), 1.88 - 2.03 (m, 1H), 2.77 - 2.97 (m, 2H), 3.45 - 3.76 (m, 2H), 6.41 - 6.58 (m, 1H), 7.64 - 7.77 (m, 1H), 7.87 (bs, 1H), 7.90 - 7.98 (m, 1H), 8.18 - 8.40 (m, 1H), 8.58 - 8.79 (m, 1H), 10.46 (bs, 1H). 267 201130835 Airlift: 0·95 Moer) 0 Bumor) and Ethene 3-(4_[(Piperidine)

The mixture was searched for 16 hours at ambient temperature. J time. The mixture was evaporated in vacuo, 4% aqueous sodium bicarbonate, water, &lt;RTI ID=0.0&gt;&gt; In a solution of ~# (4 ml) and then dissolved in two gas and the organic layer was washed with 4% aqueous solution of sodium hydrogencarbonate: water, dried (MgSO.sub.4) and evaporated. By flash layer to 96:4. Two fields are in / field knot, from, dried (MgS〇4) and evaporated. The residue was purified by EtOAc EtOAc (EtOAc:EtOAc LRMS (m/z): 376 (M+l)+. H-NMR δ (DMSO-sentence: 1.H - L88 (m, 6H), 2 3H), 3.46 - 3.95 (m, 2H) 4.14 - 4.31 (m, ih), 4.29 _ 4 51 (m old) , 4.95 (bs, 1H), 6.26 - 6.60 (m, 1H), 7.62 - 7.82 (m 1H)' 7.85 · 8.03 (m, 1H), 8.11 - 8.35 (m, 1H), 8.49 - 8 73 (mm, , 10.39 - 10.65 (m, 1H) ' ), Example 19 3-[4-(tetrahydro-2 ugly-pyran-4-ylaminopyridin-2-yl)imidazolium^ 2 acridine·6-A Nitrile

According to the experimental procedure as described in Preparation 5a, from 3_(4_base-based 268 201130835-2-yl) oxazolo[l,2-a]pyridine-6-carbonitrile (Preparation 4b) and four gases • 2 tablets of megbrane-4-amine hydrochloride gave a white solid (11 〇 / 〇)' followed by reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 acetonitrile / methanol) The crude product was purified as a scavenger [0% to 1% by weight of 0.1% v/v formic acid). LRMS (m/z): 321 (M+l)+ 〇

!H-NMR δ (CDC13): 1.65 (d, 2H), 2.12 (d, 2H), 3.64 ((J 2H), 4.07 (d, 2H), 5.03 (bs, 1H), 6.26 (bs, 1H) , 7.U (dm), 7.41 (dd, 1H), 7.79 (d, 1H), 8.27 (bs, 1H), 8.58 (bs, eg ' 10.54 (bs, 1H) ' Example 20 3-(4-( 8-fluoro-1-decane-4-ylamino)pyrimidine_2-yl)imidazolium ,j,2 bite-6-gambling

According to the experimental procedure as described in Preparation 5a, it is made from 3·(4-_-2-yl)-salt and [1,2♦ than biting _6•carbonitrile (preparation and ^ dihydropropan 1 〇) Amines (such as w〇2__i9, obtained a white solid (8%), then by reading Acacia 4, # 鸯C-18 dioxide, water / 14 B p 曰 来自 from Waters - choose. 1 The acetonitrile-methanol was used as a dissolving agent [0% to 100% by formic acid buffer) to purify the crude product. *1/〇7 269 201130835 LRMS (m/z): 387 (M+l)+. H-NMR δ (CDC13): 1.75 (bs, 1H), 2.46 - 2.26 (m, 2H), 4.51 - 4.30 (m, 2H), 6.32 (d, 1H), 6.87 (td, 1H), 7.11 - 7.02 (m, 2H), 7.42 (dd, 1H), 7.80 (d, 1H), 8.34 (d, 1H), 8.61 (s, 1H), 10.57 (s, 1H). Example 21 3-[4-(Cyclohexylamino)pyrimidin-2-yl]imidazo[l,2-fl]pyridine-6-indolecarbonitrile

Obtained as an off-white solid from 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]pyridin-6-indolecarbonitrile (Preparation 4b) and cyclohexylamine according to an experimental procedure as described in Preparation 5a (53%), then water was added and extracted with ethyl acetate. The organic layer was washed with water and brine, dried (MgSO4) and evaporated. The residue is purified by flash chromatography (99:1 to 98:2 dichloromethane). LRMS (m/z): 319 (M+l) +. !H-NMR δ (CDC13): 1.13 - 1.40 (m, 6H), 1.39-1.51 (m, 1H), 1.64 - 1.77 (m, 1H), 1.77 - 1.89 (m, 2H), 1.95 - 2.25 (m , 2H), 6.21 (d, 1H), 7.41 (d, 1H), 7.77 (d, 1H), 8.15 - 8.37 (m, 1H), 8.58 (s, 1H), 10.54 (s, 1H) Example 22 270 201130835 3-{4-[(trans-4.hydroxycyclohexyl)amino]pyrimidin-2-yl}imidazo[1,2-α] 0 ratio bite-6-method

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[l,2-a]pyridine-6-carbonitrile (Preparation 4b) and trans-4-amino Cyclohexanol obtained solid (17%), followed by reverse phase chromatography (from Waters C-18 cerium oxide, water / acetonitrile / decyl alcohol as eliminating agent [0.1% v/v formic acid buffer] 0 The crude product was purified from % to 100%). LRMS (m/z): 335 (M+l)+. ^-NMR δ (CDC13): 1.61 - 1.32 (m, 4H), 2.17 (dd, 4H), 2.67 - 2.61 (m, 1H), 3.73 (ddd, 1H), 6.23 (d, 1H), 7.40 (dd , 1H), 7.79 (d, 1H), 8.27 (d, 1H), 8.58 (s, 1H), 10.54 (s, 1H). Example 23 3-{4-[(5-Hydroxy-2-adamantyl)amino]pyrimidin-2-yl}imidazo[1,2_ίφ pyridine_6-carbonitrile

271 201130835 Borrow: Reverse phase chromatography] (purine - sterol = is a lysing agent [via 〇.1% v / v citrate buffer] 〇% to brain) purification. LRMS (m/z): 387 (M+l)+. Example 24 3_{4-[(S-Hydroxy-2-adamantyl)amino]pyrimidin-2-ylimidazolium [l,2-n]»»比咬-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, the sputum was sprayed by 3 Pu's base and [U♦ than the bite of i-carbonitrile (preparation) and (7) 4-amino 2% [3.3.1.13'7] oxime (Preparation 41) Obtained solid (6%), followed by reverse phase chromatography (from Waters c.18 dioxide, water/1:1 B.-sterol as the eliminator). ν/ν 曱 acid buffer] 〇% to 1〇〇%) purified. LRMS (m/z): 387 (M+l) + 〇H-NMR δ (CDC13): 2.00 - 1.64 (m, 13H), 6.26 (d, 1H), 7-42 (dd, 1H), 7.82 ( d, 1H), 8.27 (d, 1H), 8.58 (s, 1H), 10.51 (s, 1H). 272 201130835 Example 25 porphyrin_2-yl}imidazolium 2-{4_[(2,2-dipropylpropyl)amino] quinazozole 吼-6-A guess

Obtained according to the experimental procedure as described in Preparation 5a, from 3♦-based oxalyl-2-yl)imidazo[u♦ than biting winter carbonitrile (preparation tear) and Μ·dimercaptopropionide·amine The steroid (Μ%)' is then used as a dissolving agent by the reverse phase layer C-18 dioxide, water/1:1 acetonitrile·methanol [0.1% ν/νcarboxylic acid buffer] 〇% to ι〇 〇〇/0) The crude product was purified. LRMS (m/z): 357 (M+l)+. ^-NMR δ (CDC13): 1.11 (s, 9H), 3.67 (d, 2H), 5.87 (t, 2H), 7.42 (dd, 1H), 7.49 (ddd, 1H), 7.75 _ 7.70 (m, 1H) ), 7.83' -7.76 (m, 2H), 7.97 7.91 (m, 1H), 8.70 (s, 1H), 10.88 (dd, 1H), Example 26 3] 4-[benzyl(methyl)amino group 】 鸣 :: base} imidazole and U, 2_a] bite -6-eye 273 201130835

The dried resealable Schlenk tube was filled with sodium saliva and [l,2-a]° bite-6-carbonitrile (preparation 0.30 g, 2.1 mmol), N-benzoinyl- 2-Chloro-N-mercaptopyrimidine-4-amine (preparation 31, 0.24 g, 1.0 mmol), potassium acetate (0.21 g, 2.1 mmol) and dimethylacetamide (3 mL). The Schlank tube was subjected to three evacuation-cycles backfilled with argon followed by hydrazine (triphenylphosphine)palladium(0) (0.12 g, 0.10 mmol). After three additional evacuations - after argon backfilling, the Schlenk tube was capped and placed in a 150 ° C oil bath and the mixture was stirred overnight. The mixture was evaporated in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed with EtOAcqqHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 30%). LRMS (m/z): 341 (M+l)+. H-NMR δ (CDC13): 3.22 (bs, 3H), 4.91 (bs, 2H), 6.40 (d, 1H), 7.27 - 7.41 (m, 6H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.59 (s, 1H), 10.49 (bs, 1H) ~ Example 27 3-(4-{[(lS)-l-phenethyl]amino}pyrimidin-2-yl)imidazo[1, 2-α】bite-6-formic acid 274 201130835

3-[4-((5&gt;1-Phenyl-ethylamino)-pyrimidin-2-yl]-imidazo[l,2-a]pyridin-6-indolecarbonitrile (Example 1, 0.037 g, 0.11 Mix a mixture of potassium pentoxide (0.033 g, 0.59 mmol) in ethylene glycol (0.5 mL) to 150 ° C and stir overnight. The mixture was then cooled to room temperature and water (5 mL) And the mixture was extracted with EtOAc. EtOAc (EtOAc m. %) LRMS (m/z): 360 (M+1)' 358 (M-Ι)·. W-NMR δ (DMS0-4): 1.51 (d, 3H), 5.43 (bs, 1H), 6.46 (d, 1H), 7.20 (d, 1H), 7.31 (t, 2H), 7.50 (d, 2H), 7.73 (d, 1H), 7.83 (d, 1H), 8.13 (d, 1H), 8.18 ( d, 1H), 8.36 (s, 1H), 10.63 (bs, 1H) Example 28 2_(6-fluoroimidazo[l,2-a]&quot;bipyridin-3-yl)-7V-[(15&gt; 1-phenylethyl]pyrimidine-4-amine b, 275 201130835

a) according to the experimental procedure as described in Preparation μ, from [1,2-·bipyridine (Preparation 2, 〇.127 g' 〇93 mmol), 2 气 ··曱 曱 曱 [ [ [ (10) Small phenethyl]coholamine (preparation 3 〇 0.300 g '0.85 mmol), potassium acetate (〇138 g, i 4i mmol =) and 肆 (triphenylphosphine) palladium (0) (〇 〇98 g, 〇〇8 mmol.) 2-(6·fluoroimidazo[ΐ,2-α]pyridine_3_yl)_#_(4_methoxybenzyl) as a colorless oil )·Α4(15&gt;1-Phenylethyl]pyrimidine_4_amine (〇〇2^g, 8%). The crude product was purified by flash chromatography (1:1 hexane/ethyl acetate). m/z): 454 (M+l)+. iH-NMR δ (CDC13): 1.68 (d, 3Η), 3.78 (s, 3Η), 4.41 · 4.69 (m, 3H), 6.20 (d, lH) , 6.84 (d, 2H), 7.11 (d, 2H), 7.14 - 7.24 (m, 1H), 7.26 - 7.39 (m, 5H), 7.64 - 7.69 (m, 1H), 8.22 (d, 1H), 8.52 (s, 1H), 9.81 (bs, 1H). ' b) Stir L(6_fluoroimidazole and bite _3·yl)#(4-decylphenylphenylphenethyl)pyrimidine in a sealed tube a mixture of _4_amine (0.029 g '0.06 mmol) and trifluoroacetic acid (4 mL) and heated to 65 After a period of 19 hours, the mixture was evaporated in vacuo and EtOAc EtOAc (EtOAc m. Evaporation and purification of 276 201130835 residue by flash chromatography (100:1 to 50:1 di-methane/methanol) followed by reverse phase chromatography (from Waters C-18 cerium oxide, water/1) The title compound (0.009 g, 42%) was obtained as a white solid. EtOAc (m/z): 334 (M+l)+. ^-NMR δ (DMSO-i/6): 1.56 (d, 3H), 5.29 (bs, 1H), 6.52 (bs, 1H), 7.17 - 7.31 (m, 1H), 7.30 - 7.43 (m, 2H), 7.49 (d, 2H), 7.52 - 7.61 (m, 1H), 7.73 - 7.88 (m, 1H), 8.21 (d, 2H), 8.37 (bs, 1H), 9.78 ( Bs, 1H). Example 29 trans-4-{[2-(6-fluoroimidazo[1,2-indolylpyridin-3-yl)pyrimidin-4-yl]amino}cyclohexanol

According to the experimental procedure as described in Preparation 5a, from 2-(6-fluoroimidazo[1,2-β]pyridin-3-yl)pyrimidin-4-ol (Preparation 8b) and trans-4-amino ring The hexanol was obtained as a yellow solid (70%), then the crude material was purified by flash chromatography (dihexane / methanol: 100:10). LRMS (m/z): 328 (M+l)+. ^-NMR δ (CDC13): 1.38 (dd, 2H), 1.51 (dd, 2H), 2.08 (d, 2H), 2.20 (d, 2H), 3.67 (s, 1H), 5.74 (d, 1H), 6.22 (d, 1H), 277 201130835 7.29 - 7.16 (m, 1H), 7.73 - 7.59 (m, 1H), 8.19 (s, 1H), 8.50 (s, 1H), 10.02 (s, 1H). Example 30 3-(4-{[(2S,75&gt;5-Hydroxy-2-adamantyl]amino}pyrimidin-2-yl)mi-[1,2-ii]D ratio bite-6-A Nitrile

According to the same experimental procedure as described in Preparation 5a, except that the reaction was carried out at 60 ° C, 2-(6-fluoro-salt [1,2-«]° than 唆-3-yl) mouth bite-4 - Alcohol (Preparation 8b) and (4S,75)-4-aminotricyclo[3.3.1.13,7]nonan-1-ol gave a solid (30%). The crude product was purified by flash chromatography (9:1 dichloromethane / methanol). LRMS (m/z): 380 (M+l)+. H-NMR δ (DMSO-i/6): 1·〇9 (bs, 1H), 1.40 - 2.02 (m, 10 H), 1.63 (bs, 1H), 2.10 (bs, 1H), 2.29 (bs , 1H), 4.07 (bs, 1H), 4.46 (s, 1H), 6.56 (d, 1H), 7.53 (d, 1H), 7.81 (dd, 1H), 8.13 (d, 1H), 8.37 (s, 1H), 9.96 (bs, LH) Example 31 7V-(2,2-Dimethylpropyl)·2·imidazo[1,2·α]pyridin-3-ylpyrimidine-4-amine 278 201130835

NH obtained an off-white solid (45%) from 2-imidazo[1,2-β]pyridin-3-ylpyrimidin-4-ol (Preparation 14b) and pentylamine according to the procedure as described in Preparation 5a. The water bar was then added and extracted with ethyl acetate. The organic layer was washed with EtOAcqqqqqqqqqqqqqqqqqqqqqqqQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQQ 1H), 7.18 !Η), 8.17 iH-NMR δ (DMSO-4): 1.01 (s, 9H), 6 48 (d, (t, 1H), 7.49 - 7.39 (m, 1H), 7.55 ( t,1H), 7.77 (d (s,1H), 8.39 (s,1H), 10.08 · 9·92 (m,1H). Example 32 7V-(2,2-diylpyrimidin-4-aminepropane Base)_2_味味和[1,2·啦唆-3-基如比 bit·3

Diisopropylethylamine (0.07 ml, decylamine (0.05 ml, 0.42 mmol), ^^, 斗), and 新. Ear) Yang to _ mix 3 (4' qi 279 201130835 G ) 蝴 以 嚏 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 制 27 27 制 制 27 27 = = = = = = = = = = = = = = = 二 = = = ϋ 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发 发LRMS (m/z): 359 (M+l)+. ^-NMR δ (CDC13): 1.07 (s, 9H), 3.29 (s, 2H) 5 25 Ts 1H), 6.61 (s, 1H), 7.00 (t, 1H), 7.38 - 7.29 (m, 1H), 7.47 (dd! 1H), 7.74 (d, 1H), 8.40 - 8.33 (m, 1H), 8.61 (Sj ih), 8.73 (dd, 1H), 9.28 (s, 1H), 10.04 (d, 1H). Example 33 3-(6-{[(15&gt;l-phenethyl]amino}pyrazine-2-yl)isoxazole, 2 sec-pyridine-6-carbonitrile ’

According to the same experimental procedure as described in Example 26, from 6-gas _^_(1_phenethyl)pyrazin-2-amine (preparation 32) and imidazolium uj-a] pyridine-6 carbonitrile (preparation) 1) Obtained a green solid (73%). The crude product was subsequently purified by flash chromatography (99:1 to 98:2 dioxane / methanol). LRMS (m/z): 341 (M+l)+. 280 201130835 !H-NMR δ (CDC13): 1.69 (d, 3H), 5.04 (t, 1H), 5.21 (d, 1H), 7.27 - 7.32 (m, 1H), 7.34 - 7.51 (m, 5H), 7.75 (d, 1H), 7.81 (s, 1H), 8.25 (s, 1H), 8.33 (s, 1H), 10.06 (s, 1H) Example 34 3-{6-[(cyclohexylmethyl)amino Bupyrazin-2-yl}imidazo[1,2 is called acridine-6-method

According to the experimental procedure as described in Preparation 5a, from 3-(6-hydroxypyrazin-2-yl)imidazo[1,2-a]pyridine-6-indoleonitrile (Preparation 29, 0.052 g, 0.22 mmol) The ear) and cyclohexylmethylamine (0.11 mL, 0.88 mmol) afforded a solid (26%). LRMS (m/z): 333 (M+l)+. ^-NMR δ (DMSO-d6): 0.97 - 1.13 (m, 2H), 1.25 (bs, 4H), 1.74 (bs, 4H), 1.91 (d, 1H), 3.27 (t, 2H), 7.57 (t , 1H), 7.69 (d, 1H), 7.88 - 7.96 (m, 1H), 8.40 (s, 1H), 8.61 (s, 1H), 10.41 (s, 1H) Example 35 6-(6-fluoroimidazolium [1,2-&lt;i]pyridin-3-yl)-7V-[(15)-l-phenethyl]pyr-2-amine 281 201130835

*, (1 alntb phenethyl) ° azine-2-amine (preparation 32) and 6-fluoroimidazo[2] According to the experimental procedure as described in Example 26, green was obtained from qi 2 (preparation 2) Solid (25%), followed by reverse phase layer of Whitewater C-18 dioxide, water/1:1 acetonitrile-methanol [0.1% v/v citrate buffer] 0% to 100 〇/〇) Purify the crude product. LRMS (m/z): 334 (M+l)+. H-NMR δ (CDC13): 1.66 (d, 3H), 5.01 - 5.12 (m 2H) 7.15 - 7.23 (m, 1H), 7.33 - 7.46 (m, 5H), 7.63 (dd, 1H), 7.75 ( s, 1H), 8.15 (s, 1H), 8.28 (s, 1H), 9.39 (dd, 1H), Example 36

6_(6-azamidazo[1,2·α]pyridine each)_#·[(10)M phenethyl 嗓-2-amine J

According to the experimental procedure as described in Example 26, from (5 &gt; 6 _ gas (1 phenethyl). Peak 2 - amine (preparation of cut and 6 _ gas and [u · bite 282 201130835 (preparation 3) The green solid (71%) was obtained, then the crude material was purified by flash chromatography (99:1 to 97:3 m. methane / methanol). LRMS (m/z): 350 (M+l)+. H-NMR δ (CDC13): 1.60 (s, 3H), 5.08 (bs, 2H), 7.29 (bs, 2H), 7.37 (t, 2H), 7.41 - 7.50 (m, 1H), 7.64 (d, 1H) ), 7.75 (s, 1H), 8.16 (s, 1H), 8.30 (s, 1H), 9.72 (s, 1H) Example 37 〇S&gt;6-(imidazo[l,2-a] 3-yl)-N-(l-phenethyl) morphine

To 6-(6-chloroimidazo[ι,2·α]acridin-3-yl)-Aq(15&gt;l-phenethyl]pyrazin-2-amine (Example 36, 0.100 g, 0.29 mmol) Add 1 〇〇 / 0 palladium / charcoal (0.006 g) and formic acid (0.180 g '2.9 mmol) to the solution. The mixture was stirred and heated to reflux for 24 hours. Further, palladium (0.006 g) and ammonium formate (〇18 g) were added and stirring was continued for 24 hours under reflux. This process is repeated until very little starting material remains. The reaction mixture was then filtered, evaporated and subjected to reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-nonanol as the eliminator [via 0.1% v/v citric acid buffer] 〇 The title compound (0.023 g, 25%). 283 201130835 LRMS (m/z): 316 (M+l)+. 'H-NMR δ (CDC13): 1.64 (d, 3H), 5.00 (bs, 2H), 6.66 (t, 1H), 7.28 - 7.34 (m, 0 H), 7.40 (bs, 4H), 7.65 (d , 1H), 7.78 (s, 1H), 8.10 (s, 1H), 8.27 (s, 1H), 8.95 (d, 1H) Example 38 6-(6-cyclopropylimipro[l,2-d ]nb -3-yl)phenethyl]° 嘻-2-amine

Nitrogen gas was bubbled through the microwave container (5 &gt; 6-(6- oxazolo[l,2_a]n ratio bite_3·yl)-Ν·(1_phenethyl)pyrazine-; 2-amine (Example 36, 0.085 gram, 0.24 house mole), cyclopropylboronic acid (〇〇81 g, 〇94 mmol) and potassium phosphate (〇.180 g, 0 85 mmol) in toluene (1 〇 ml) and a mixture of water (0.1 ml) towel 5 palladium acetate (11) (0.004 g, 〇〇 1 m Mous 搔 夺 夺 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客 客(0.014 mg, .05 mmol), the vessel was sealed and allowed to stand for 7 hours. The reaction was partitioned between dichloromethane m/microprops/1:1 acetonitrile-methanol as the dissolving agent [via _18-yttria] The residue was purified to give the title compound 284, </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> 356 (M+l) )+. !H-NMR δ (CDC13): 0.73 (bs, 2H), 0.99 (d, 2H), 1.69 (d, 3H), 1.87 (bs, 1H), 4.95 (d, 1H), 5.05 - 5.25 (m, 1H), 7.00 (d, 1H), 7.28 - 7.48 (m, 5H), 7.59 (d, 1H), 7.69 (d, 1H), 8.10 (d, 1H), 8.29 (d, 1H), 9.42 (s , 1H) Example 39 7ν·[(1Λ&gt;1-Phenylethyl]-6-(6-pyridin-3-ylimidazo[1,2-fl]pyridin-3-yl)etb^-2-amine

Nitrogen gas was bubbled through the 〇S&gt;6-(6-azamidazo[l,2-a]pyridin-3-yl)-indole 1-phenylethyl)pyrazine-2-amine contained in the microwave vessel (example) 36, 0.080 g, 0.23 mmol, pyridin-3-ylboronic acid (0.056 g, 0.46 mmol) and potassium carbonate (0.063 g, 0.46 mmol) in 1,4-dioxane (1.0 mL) And a mixture of ethanol (0.5 ml) for 5 minutes. Next, ruthenium (triphenylphosphine)palladium(0) (0.026 g, 0.02 mmol) was added, and the vessel was sealed and subjected to microwave irradiation at 150 ° C for 3 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was dried <RTI ID=0.0>(M </RTI> <RTI ID=0.0> 45%). LRMS (m/z): 393 (M+l)+. W-NMR δ (DMS0-4): 1.48 (d, 3H), 5.14 (five-peak, 1H), 7.08 - 7.18 (m, 4H), 7.58 (ddd, 1H), 7.70 - 7.86 (m, 4H) , 7.90 (s, 1H), 8.16 (ddd, 1H), 8.41 (d, 2H), 8.70 (dd, 1H), 8.99 (dd, 1H), 10.01 (dd, 1H) Example 40 TV-[(15) -1-phenethyl]-6-(6-°pyridin-4-ylimidazo[l,2-ii] acridine-3-ylqin-2-amine

According to the experimental procedure as described in Example 39, from (5)-6-(6-azamidazo[l,2-a]acridin-3-yl)-N-(l-phenylethyl carbazine) 2-Amine (Example 36) and 4-(4,4,5,5-tetradecyl-1,3,2-dioxaborin |-2-yl)pyridine gave a solid (36%), which was subsequently The crude product was purified by flash chromatography (98:2 to 95:5 dioxane / decyl alcohol). LRMS (m/z): 393 (M+l) +. 'H-NMR δ (CDC13): 1.65 (d, 3H), 5.00 (d, 1H), 5.16 (t, 1H), 7.46 - 7.58 (m, 3H), 7.74 (s, 1H), 7.82 (d, 1H), 8.21 (s, 1H), 8.35 (s, 1H), 8.69 (d, 2H), 10.00 (s, 1H) 286 201130835 Example 41 7V-[(1S)-1-Phenylethyl]_6-丨6-(1 and -°-pyrazole- 4_base) imidazo[1,2-ί!] 0 is more than -3-yl] π than indole-2-amine

According to the experimental procedure as described in Example 39, from (5&gt;6-(6-chloroimidazo[1,2-a]acridin-3-yl)-N-(l-phenylethyl)-pyrazine 2-Amine (Example 36) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxabor04-2-yl)-1Η-«biazole gave a pale green solid ( 23%), then the crude product was purified by flash chromatography (98:2 to 96:4 di-methane/methanol). LRMS (m/z): 382 (M+l)+.]H-NMR δ ( DMSO-4): 1-61 (bs, 3H), 5.26 (bs, 1H), 7.14 - 7.46 (m, 5H), 7.64 - 8.48 (m, 7H), 9.94 (bs, 1H) Example 42 7V-[ (LS&gt; 1-phenethyl)-6-(6-phenylimidazopyridin-3-yl)pyrazin-2-amine 287 201130835

According to the experimental procedure as described in Example 39, from 〇S&gt;6-(6-chloroimidazo[l,2-a]acridin-3-yl)-AK1-phenylethyl-carbazine-2-amine (Example 36) and phenylboronic acid afforded a light green solid (38%), which was subsequently purified by flash chromatography (98:2 to 97:3 dichloromethane / methanol). LRMS (m/z): 392 (M+l)+. H-NMR δ (CDC13): 1.25 (bs, 3H), 4.96 (bs, 1H), 5.15 (bs, 1H), 7.35 (bs, 7H), 7.40 - 7.86 (m, 5H), 8.19 (bs, 1H), 8.34 (bs, 1H), 8.76 (bs, 1H), 9.93 (bs, 1H) Example 43 6_[6-(4-Fluorophenyl)imidazo[l,2_ii]pyridin-3-yl] -7V-[(15&gt;1-phenethyl]pyrazin-2-amine

According to the experimental procedure as described in Example 39, 〇S&gt;6-(6-chloroimidazole 201130835 and [1,2-3]0 ate-3-yl)-_/^-(1-phenylethyl) 〇 〇 嗅 _2 _ 胺 ( ( (Example 36) and 4-fluorophenylboronic acid obtained a light green solid (32%), followed by flash chromatography (98:2 to 97:3 dichloro decane / decyl alcohol) The crude product was purified. LRMS (m/z): 410 (M+l)+. ^-NMR δ (CDC13): 1.58 (s, 3H), 2.18 (s, 1H), 7.17 (t, 1H), 7.22 - 7.30 (m, 9H), 7.46 - 7.60 (m, 1H), 7.76 (dd , 1H), 8.19 (s, 1H), 8.33 (s, 1H), 9.86 (dd, 1H) Example 44 3-(4_{[(3 and)-1-(B)-based bite_3· Imidazo][1,2-α]pyridine-6-carbonitrile

Triethylamine (0.064 ml, 0.46 mmol) and ethyl helium (0.032 ml, 0.34 mmol) were sequentially added to the cooled (ice bath) and stirred 3-{4-[(3) /?&gt; Piperidinylamino]pyrimidin-2-yl}imidazo[1,2-α]pyridine-6-carbonitrile (Preparation 5b, 0.072 g, 0.23 mmol) - dichloromethane (3 The mixture was allowed to warm to ambient temperature and stirred for 3 h. then water was added and the organic layer was washed with water and brine, dried (MgSO & evaporated and evaporated The title compound (0.052 g, 56%) was obtained as a white solid. 289 s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s (m, 4H), 1.94 (s, 4H), 3.08 - 2.87 (m, 3H), 3.49 (s, 3H), 5.33 (s, 1H), 6.32 (s, 1H), 7.77 (d, 1H), 8.27 (s,1H), 8.60 (s,1H), 10.55 (t, 1H). Example 45 3-(4-{[(3i?)-l-(isopropylsulfonyl)piperidin-3-yl Amino}pyrimidin-2-yl) is astringent and [1,2_α]0 is more than bite-6-carbonitrile

According to the same experimental procedure as described in Example 44, from 3-{4-[(3)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-α]pyridine-6 - mercaponitrile (preparation 5b) and propane-2-sulfonium chloride to give a solid (18%). Purification of the crude product by reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-nonanol as the eliminator [0.2% v/v formic acid buffer] 0% to 100%) . LRMS (m/z): 426 (M+l)+. *H-NMR δ (CDC13): 1.37 (dd, 6H), 1.67 - 2.09 (m, 4H), 2.88 - 2.98 (m, 1H), 3.22 (dt, 1H), 3.70 (bs, 4H), 5.41 ( Bs, 1H), 6.35 (bs, 1H), 7.40 (d, 1H), 7.79 (d, 1H), 8.28 (bs, 1H), 8.61 (s, 1H), 10.55 (s, 1H) Example 46 3- (4-{[(3i?)-l-(cyanoethyl)piperidin-3-yl]amino}pyrimidin-2-yl) 290 201130835 Taste and U, 2 outside &amp; «A guess

In the order of triethylamine (0.10 ml, bismuth oxypyrrolidine J gan, open 〇 · 72 mM) and Μ (2,5-(Α1) 遨 - -) oxalate]-3 - side oxypropionitrile (such as ΒΕ875〇Μ _6-carbonitrile (preparation 5b, what is H·2· base and [1, 2♦ than bite (5 ml), Xuan Panqin 0.63 millimolar) Dichloromethane is secretive. ~. At ambient temperature _ mixture for 24 hours, pick up the water and extract the mixture with trichloromethane. Dry (Mgs 〇 4) 曰 'evaporate and by flash chromatography (98 The residue was purified by EtOAc (EtOAc: EtOAc (EtOAc) NMR δ (DUSO-d6): 1.67 - 1.49 (m, 2H), 1.89 - 1.70 (m, 2H), 2.11 - 1.98 (m, 2H), 2.51 (s, 2H), 3.66 (t, 1H), 3.90 (t, 1H), 4.66 (d, 1H), 6.44 (d, 1H), 7.69 (dt, 1H), 7.90 (ddd, 1H), 8.23 (s, 1H), 8.61 (s, 1H). 3-(4-{[(3i〇-l-propyl-propylpiperidin-3-yl)amino}pyrimidin-2-yl)imidazole 291 201130835 and [1,2-έΐ]0 ratio bite-6·A Nitrile

In a sequential order, triethylamine (0.024 ml, Q 17 gas (0.036 ml, 0.42 苴 苴 and &gt;, 耄 耄 ear) and 醯 醯 -3- -3- 基 基 基 · · 基 基 基 , , , , (4) gm, lenonitrile (prepared. The mixed ear is found at ambient temperature and the residue is dissolved in dichloromethane φ: both evaporate in the real work. Λ, c„, ^ gas decane The organic layer was washed with water and brine, dried (MgSO.sub.4), and the residue was dissolved in 2 m aqueous hydrochloric acid and washed with ethyl acetate. The aqueous layer was neutralized with 2 M aqueous sodium hydroxide and extracted with methane. The title compound (0.032 g, 54%) was obtained as a white solid. </ RTI> </ RTI> RMS (m/z): 376 (M+l) +. ^-NMR δ (DMSO-4) : 4.74 (d, 1H), 6.47 (d, 1H), 7.72 (s, 2H), 7.91 (d, 1H), 8.24 (s, 1H), 8.57 (d, 1H), 10.47 (s, 1H). Example 48 3-[4-({(3π)-1-[(1-Cyanocyclopropyl)carbonyl)piperidin-3-yl}amino)pyrimidin-2-yl]imidazo[1,2- /1]pyridine-6-carbonitrile 292 201130835

U'-Carbonyldiimidazole (0.040 g, 0.25 mmol) was added to a stirred solution of 1-cyanocyclopropanecarboxylic acid (0.041 g, 0.37 mmol) in di-hexane (1 mL). After stirring at ambient temperature for 15 minutes, 3-{4-[(3i?)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-α]pyridine-6-A was added. Nitrile (preparation 5b, 0.040 g, 0.13 mmol) and the mixture was stirred overnight. The mixture was evaporated and purified EtOAcjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj LRMS (m/z): 413 (M+l)+. !H-NMR δ (CDC13): 2.04 - 1.44 (m, 8H), 2.20 (s, 1H), 3.73 - 3.50 (m, 1H), 4.44 - 3.88 (m, 2H), 5.08 (bs, 1H), 6.35 (bs, 1H), 7.42 (dd, 1H), 7.79 (dd, 1H), 8.32 (d, 1H), 8.64 (s, 1H), 10.54 (s, 1H). Example 49 3--(4·{[(3Λ)-1-(methoxyethenyl)piperidin-3-yl]amino}pyrimidin-2-yl)indolo[1,2-β] 0 than bite-6-A guess 293 201130835

According to the experimental procedure as described in Example 48, an off-white solid was obtained from 夂b_3_ylamino]pyrimidin-2-yl}-oxazolopyridine 4-method 3 and), pyridine and 2-methoxyacetic acid ( 57〇/〇). ^ Purified crude by Preparation 5b) (C-18 from Waters, acetonitrile-methanol, acetonitrile, 1% ν/ν citrate buffer, 0% to 1%) product. 'Fighting LRMS (m/z): 392 (M+l)+. W-NMR δ (CDC13): 1.57 (s, 3Η), 2.19 - 1.60 (m, 4Η), 2.92 (d, 1H), 3.43 (s, 2H), 4.14 (d, 2H), 5.54 - 4.96 (m , 1H), 6.30 (s, 1H), 7.39 (d, 1H), 7.77 (d, 1H), 8.28 (d, 1H), 8.59 (s, 1H), 10.52 (s, 1H) ° Example 50 3- (4-{[(3Λ)-1-(3-hydroxy-3-methylbutyryl)piperidin-3-yl]amino}pyrimidin-2-yl)imidazo[1,2-pyridyl-6 -carbonitrile

294 201130835 According to the experimental procedure as described in Example 48, by 3_{4·[(3/?)-η bottom bite 3-3-aminol group] bite-2-yl}° 嗤 and [1,2 -α]η gave an off-white solid (23%) over _6_carbonitrile (preparation 5b) and 3-hydroxy-3-methylbutyric acid. By reverse phase chromatography (from Waters C-18 cerium oxide, water / 1: acetonitrile - methanol as a dissolving agent [0. 1% v / v citrate buffer] 〇% to ι 〇 0% The crude product was purified. LRMS (m/z): 420 (M+l)+. ^-NMR δ (CDC13): 1.33 (d, 6H), 1.65 - 1.97 (m, 4H), 2·14 (bs, 1H), 2.55 (s, 2H), 3.31 - 3.96 (m, 2H), 5.04 - 5.18 (m, 2H), 6.29 (d, 1H), 7.40 (d, 1H), 7.80 (t, 1H), 8.30 (d, 1H), 8-56 (s, 1H), 8.62 (s, 1H) ), 10.54 (s, 1H) 'Example 51 3-(4·{[(3Ι?)-1-(3,3-dimethylbutyryl))-amino]ylamino]pyrimidine- 2-base) miso and [ι,2-ίΐ] 0 to bite-6-carbonitrile

According to the experimental procedure as described in Example 48, from 3_{4·[(3Λ)-Slightly -3-amino-amino] σ 定 _2 - _2 _2 _2 唾 ι ι ι ι ι ι ι ι ι ι ι ι The acetonitrile (preparation 5b) and 3,3-dimercaptobutyric acid gave an off-white solid. Purified by reverse phase chromatography (to 295 201130835 from Waters C-18 cerium dioxide 'water / 1:1 acetonitrile-methanol as a dissolving agent [0.1% v/v formic acid buffer] 〇% to 100%) Crude product. LRMS (m/z): 418 (M+l)+. iH-NMR δ (CDC13): 0.99 (s, 9H), 1.71 (bs, 2H), 1.84 (bs, 2H), 2.13 (bs, 2H), 3.38 (bs, 1H), 3.65 (bs, 2H), 3.96 (bs 2H), 5.14 - 5.24 (m, 1H), 6.26 (d, 1H), 6.29 - 6.40 (m, 1H) ' 7.41 (t, 1H), 7.79 (s, 1H), 8.23 - 8.35 (m ,1H),8.61 (s,1H) '

Example 52, J-based) 3-(4-{[(3))-1-(1 oleazole-4-ylethylpyrimidin-2-yl) oxazole Pyridyl-6-carbonitrile

Diethylamine (0.15 ml, taste saliva (five) 28 g, 丨.1 mmol) and 1,1,_carbonyl II

Analysis (from Waters C-18 - dimethyl A. Under a reduced pressure, a water 296 201130835 / 1:1 acetonitrile-nonanol as a dissolving agent [via 0.1% v/v citrate buffer] The residue was purified to give the title compound (0.064 g, 32%). LRMS (m/z): 428 (M+l)+. 'H-NMR δ (OUSO-d6): 1.55 (bs, 1H), 1.73 (bs, 1H), 2.02 (bs, 2H), 2.52 - 2.66 (m, 1H), 3.02 - 3.51 (m, 2H), 3.61 (d, 2H), 3.95 (d, 1H), 4.67 (d, 1H), 6.38 - 6.55 (m, 1H), 6.87 (bs, 1H), 7.55 (s, 1H), 7.69 (d, 1H) , 7.90 (d, 1H), 8.21 (s, 1H), 8.51 (s, 1H), 8.63 (bs, 1H), 10.45 (bs, 1H) Example 53 3-[4-({(3))-1 -[(5-cyano)pyridin-2-yl)carbonyl]piperidin-3-yl}amino)pyrimidin-2-yl]imidazo[1,2_ίφpyridin-6-carbonitrile

According to the experimental procedure as described in Example 48, except that dimethylformamide was used as the reaction solvent, 3-{4-[(3 and)-pyrylene-3-ylamino]pyrimidin-2-yl was used. The imidazo[1,2·α]pyridine-6-indolecarbonitrile (Preparation 5b) and the hydrazinylpyridine-2-carboxylic acid gave an off-white solid (23%). Purification of crude by reverse phase chromatography (C-18 from Waters, water/1:1 acetonitrile-nonanol as eliminator [0.1% ν/νcarboxylic acid buffer] 〇% to 100%) product. 297 201130835 LRMS (m/z): 450 (M+l)+. ^-NMR δ (DMSO-i/6): 1.93 (m, 2H), 3.05 - 2.77 (m, 1H), 3.57 (d, 1H), 4.23 - 3.71 (m, 2H), 5.82 (s, 1H) , 6.51 (d, 1H), 7.61 - 7.36 (m, 2H), 7.86 (dd, 2H), 8.60 - 8.07 (m, 2H), 10.51 (d, 1H). Example 54 3-(4-{[(3i?)-l-(3,3,3-trifluoropropionyl)piperidin-3-yl]amino}pyrimidin-2-yl) miso[l, 2-ii]0 than bite-6-carbonitrile

Hexafluorophosphoric acid [(dimethylamino)(3//-[1,2,3]triazolo[4,54]pyridin-3-yloxy)indenyl]# diammonium (Ar '[(Dimethylamino)(3/i-[l,2,3]triazolo[4,5-6]pyridin-3-ylo xy)methylene]-iV-methyl-methanaininium hexafluorophosphate) (0.060 g, 0.16 mmol) And diisopropylethylamine (0.028 ml, 0.163⁄4 mol) was added to a stirred solution of trifluoropropionic acid (0.015 mL &lt;RTI ID=0.0&gt;0&gt; Mix the mixture at ambient temperature for 1 minute, then add M4-[(10)-h-hydroxylamino]m-yl}嗦啥 and [U-啦 bit-6-曱 guess (preparation 5b, 〇.〇5〇)克, 〇16 298 201130835 Stir the mixture overnight. Then dispense between water and dichloromethane. Wash the organic layer with water, brine, dry (MgSOO and evaporate, by strip 7 ' (98:2 to 96:4) The title compound (0.040 g, 60%) m.

b-NMR δ (CDC13): 1.47 - 1.07 (m, 2H), L 2.16 (s, 1H), 3.38 (dt, 2H), 3.93 - 3.54 (m, lH)j 5.〇〇W m, 6.30 ( s, 1H), 7.40 (d, 1H), 7.77 (d, 1H), 8.30 (s, lH) 8 ; 〇/: 1H), 10.52 (s, 1H). To .58 (d, Example 55 (10)-3-{[2-(6·Cyano-based material and like rushing 3 base) money. Amino}-Ayv-dimethylpiperidine small formamide

Add triethylamine (0.019 ml, 〇14 mM = _7 ml, millimolar) = A = :!) solution. At the ambient temperature, the factory gas of the secretory 2 was stunned (with 1 - gas chamber compound and washed with water, brine, dried: MgS〇4) 299 201130835 and evaporated. The solid was dissolved in 2N aqueous hydrochloric acid and washed with ethyl acetate. The aqueous layer was basified with 2 aqueous sodium hydroxide solution and the product was extracted with dichloromethane. The title compound (0.032 g, 65%) was obtained. LRMS (m/z): 391 (M+l)+. H-NMR δ (CDC13): 1.61 (bs, 1H), 1.85 (d, 1H), 2.89 (s, 6H), 3.31 (bs, 4H), 6.34 (bs, 1H), 7.43 - 7.32 (m, 1H), 7.77 (d, 1H), 8.20 (s, 1H), 8.58 (s, 1H), 10.59 (s, 1H). Example 56 3-{4-[((3Λ)-1-{[(25,49)·2-cyano-4_fluorolatyrridin-1-yl]carbonyl}piperidinyl-3-yl)amino] Pyrimidin-2-yl}imidazo[l,2-ii]npyridin-6-carbonitrile

Broken carbonyl)-3-methyl-1//-imidazole-3- rust (preparation 36, 0.100 g, 0.29 mmol), (and)-3-(4-(piperidine) at ambient temperature 3-aminoamine, pyrimidine-2-yl)imidazo[l,2-a]pyridin-6-carbonitrile (preparation 5b, 94 mg, 0.29 mmol) and triethylamine (0.075 ml, 0.54 m) A solution of the mixture of dichloromethane (2 mL) and dichloromethane (1 mL) was stirred overnight. The solvent was removed under reduced pressure and subjected to reverse phase chromatography (from Waters C-18 300 201130835 cerium dioxide 'water/acetonitrile/methanol as the dissolving agent [via 〇.1〇/〇v/v formic acid buffer) The residue was purified to give the title compound (m. LRMS (m/z): 460 (M+l)+. (s,1H) !H-NMR δ (CDC13): 1.62-2.13 (m, 4H), 2.24 - 2.44 (m, 1H), 2.56 (bs, 1H), 3.29 (bs, 1H), 3.55 (bs, 1H), 3.66 - 3.95 (m, 3H), 5.09 (bs, 1H), 5.21 - 5.43 (m, 2H), 6.36 (bs, 1H), 7.40 (d, 1H), 7.76 (d, 1H), 8.25 (bs, 1H), 8.56 (s, 1H), 10.53 Example 57 3-(4•川三外1(5-Cyano-pyridin-2-yl)-bistin-3-yl]amino}Nylidene Base) miso and [ι,2-&lt;ι] "ι than bite-carbonitrile

301 201130835 Dry (MgS〇4) and evaporate. The residue was purified by flash chromatography (yield: EtOAc (MeOH)MeOH) The aqueous layer was assayed with 2M aqueous sodium hydroxide and the product was extracted with dichloromethane. The organic layer was dried (M.sub.4). 2.26 - 1.65 (m, 4H), 3.48 - 3.27 (m 2H), 3.99 (dt, 2H), 4.51 (d, 1H), 5.12 (s, 1H), 6.31 (bs, IH)^ 6.69 (d, 1H ), 7.41 (dd, 1H), 7.63 (dd, 1H), 7.81 (d, 1H) 8 3〇(d, 1H), 8.41 (d, 1H), 8.62 (s, 1H), IO.54 (s , 1H) 〇' . Example 58

3-(4-{[()-1-(4-cyano)2-fluorophenyl) _3_yl]amino} mouth bite

BTS-3-ylamino] 其 \ σ 电 o / / · · · · · · · · · · · · 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Millenol) added to the stirred 3 &amp; potassium acid (0.025 g, 0.18 mmol)

201130835 night. The mixture was evaporated and the residue was crystallised eluted elut elut elut elut elut eluting % LRMS (m/z): 439 (M+l)+. W-NMR δ (CDC13): 2.06 _ 1.79 (m, 4H), 3.21 (bs, 3h 3.56 _ 3.45 (m, 2H), 5.38 (s, 1H), 6.31 (d, 1H), 7.01 (t, 3j) ^' 7.34 7.28 (m, 1H), 7.44 - 7.36 (m, 2H), 7.79 (d, 1H), 8 "(d,1H), 8.60 (s,1H), 10.56 (s,1H). , Examples 59

3H Η-[[(3Λ)-1-(cyanoethyl)piperidinyl-3-yl](methyl)amino-2-yl}carbazolo[1,2-α] Nitrile J '

Mol) ethanol U gram, 〇. 〇 9 物 48 hours, then evaporate 1 add water and use temperature / disturbance, butt dry (_ organic layer, and by - reverse special 303 201130835 world C-18 Ceria, water/1:1 acetonitrile sterol as a dissolving agent [by 〇1〇/. v/v citrate buffer] 0% to 100%), the residue was purified to give the title compound (0.013 g) , 36%). LRMS (m/z): 401 (M+l)+. !H-NMR δ (CDC13): 1.90 (bs, 2H), 2.07 (bs, 2H)} 2 73 (bs, 1H), 3.05 (bs, 3H), 3.11 - 3.24 (m, 1H), 3.68 (bs 2H) 3.78 (bs, 1H), 4.74 (bs, 2H), 6.38 (bs, 1H), 7.39 (bs, 7.78 (bs, 1H), 8.35 (bs, 1H), 8.64 (bs, 1H), 10.43 (bs, 1H), example 60,

3-(4-{[(35)-l- 嗤 嗤 比 比 比 比

According to the experimental procedure as described in Example 46, from 3_{4_[(3s), piperidin-3-ylamino]pyrimidin-2-yl}imidazo[ΐ,2-α]η is more than carbonitrile (Preparation 7^ and 3-[(2,5-di- oxypyrrolidinyl)oxy] oxy oxy) ΒΕ 〇 〇 〇 。 。 。 。 。 。 。 。 。 。 。 。 。 。 Purification of the crude product by flash chromatography (97:3 to 96:4 methylene chloride / methanol) / LRMS (m/z): 387 (M+l) + °^-NMR δ (DMSO-^): 4.11 (s, 2H), 4.72 (d, 1H), 6.49 304 201130835 (s, 1H), 8.66 (s, 1H), (d, 1H), 7.75 (d, 2H), 7.96 (d, 1H), 8.29 10.50 (s, 1H) 〇 Example 61 pyridine-3-yl]amino}pyrimidine cis-3-(4-{l-(cyanoethenyl)_4-methylanthene-2-yl) oxazole [ i,2_fl】pyridine·6_carbonitrile

According to the experimental procedure described in 5a, the 3_(4_------------------------------------------------------------------------- _ 丨 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The organic layer was washed with water, a saturated aqueous solution of sodium bicarbonate, brine, dried (MgSO4) and evaporated. [〇.1%ν/νcarboxylic acid buffer]〇% to 100%) Purification residue LRMS (m/z): 401 (Μ+ΐί)+. !H-NMR δ (CDC13): 1.07 (t, 3H), 2.26 - 2.11 (m, 1H), 3.31 (d, 2H), 3.58 (d, 1H), 4.01 (d, 1H), 4.43 (d, 1H), 4.63 (d, 1H), 5.06 - 4.93 (m, 1H), 6.35 (dd, 1H), 7.49 - 7.35 (m, 1H), 305 201130835 7.80 (dd, 1H), 8.29 (dd, 1H), 8.57 (s, 1H), 10.56 (d, 1H) Example 62 cis-3-(4-{l-(ethylsulfonyl)-4-methylpiperidin-3-yl]amino}pyrimidin-2-yl) anthracene [l,2-fl 】° ratio bite-6-indole

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[l,2-a]pyridine-6-indolecarbonitrile (Preparation 4b) and cis-1-(B) Sulfhydryl)-4-mercaptopiperidin-3-amine (Preparation 35b) gave a pale yellow solid (44%), which was then warmed to <RTIgt; After the reaction was completed, the mixture was partitioned between water and ethyl acetate. The organic layer was washed with EtOAc EtOAc m. LRMS (m/z): 426 (M+l)+. H-NMR δ (CDC13): 1.04 (d, 3H), 1.38 (t, 3H), 1.75 -1.52 (bs, 2H), 2.08 - 1.83 (m, 2H), 3.17 - 2.81 (m, 4H), 3.89 (d, 2H), 4.61 (s, 1H), 5.48 (d, 1H), 6.35 (d, 1H), 7.40 (dd, 1H), 7.77 (d, 1H), 8.22 (d, 1H), 8.55 (s, 1H), 10.54 (s, 1H). Example 63 3-{4-[[l-(ethylsulfonyl)-4-methylpiperidin-3-yl](methyl)amino]pyrimidine 306 201130835 pyridine-2-yl}imidazo[1, 2_ύτ]pyridine-6-carbonitrile

According to the experimental procedure as described in Preparation 5a, from 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]pyridine-6-indolecarbonitrile (Preparation 4b) and 1-(ethenesulfonate) The group of -N,3-dimercaptopiperidin-4-amine (Preparation 33d) gave a pale-yellow solid (31%). The crude product was purified by flash chromatography (EtOAc:EtOAc) LRMS (m/z): 440 (M+l)+. ^-NMR δ (DMSO-4): 1·〇3 (d, 3H), 1.24 (bs, 3H), 1.72 (bs, 2H), 1.91 - 2.05 (m, lH), 2.51 (bs, 3H), 3.10 - 3.21 (m, 1H), 3.23 - 3.36 (m, 4H), 3.40 - 3.40 (m, 2H), 7.86 - 7.93 (m, 1H), 8.00 - 8.07 (m, 1H), 8.41 (d, 1H ), 8.85 (bs, 1H), 10.19 (bs, 1H) Example 64 3_((3Λ)·3·{[2-(6-fluoroimidazo[1,2·ίφ-pyridin-3-yl)pyrimidine- 4-yl]amino}piperidin-1-yl)_3_sideoxypropionitrile 307 201130835

According to the experimental procedure as described in Example 46, 2-(6-fluoroimidazo[l,2-a]ntbn--3-yl)-7V-(Nymphoteric-3-yl)-negative-4 - an amine (preparation 9b) and 3-[(2,5-di- oxy π pyridin-1 -yl)oxy]-3-oxo-propanoid (prepared as described in ΒΕ875054 (Α1)) Obtained as an off-white solid (98%). Purification of the crude product by reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-nonanol as the eliminator [0% to 100% buffered with 0.1% ν/v acid) . LRMS (m/z): 380 (M+l)+. ^-NMR δ (CDC13): 1.80 (bs, 3H), 1.97 (bs, 1H), 2.16 (bs, 2H), 3.57 (s, 2H), 3.67 (bs, 2H), 5.00 (s, 1H), 6.28 (dd, 1H), 7.30 - 7.19 (m, 1H), 7.69 (td, 1H), 8.29 (t, 1H), 8.48 (s, 1H), 8.55 (s, 1H), 9.96 (ddd, 1H) . Example 65 (and)-1-(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidine-1-carbonyl) ring Propane carbonitrile 308 201130835

According to the experimental procedure as described in Example 48, from (i?)-2-(6-fluoroimidazo[l,2-a]n ratio -3-yl)-Λ^-(α辰咬-3 -Base) ♦ -4-Amine (Preparation 9b) and 1-cyanocyclopropanedecanoic acid afforded a white solid (76%). The crude product was purified by flash chromatography (100:8 dichloromethane / methanol). LRMS (m/z): 406 (M+l)+. ^-NMR δ (CDC13): 1.56 (s, 3H), 1.90 (dd, 2H), 2.19 (d, 2H), 4.34 - 4.16 (m, 2H), 4.96 (s, 1H), 6.28 (s, 1H ), 7.23 (dd, 1H), 7.68 (dd, 1H), 8.29 (d, 1H), 8.55 (s, 1H), 9.96 (d, 1H). Example 66 2-(6-Fluoroimidazo[l,2~fl]pyridin-3-yl)-7V-[(3i〇-l-(3,3,3-trifluoropropionyl)piperidin-3-yl Pyrimidine-4-amine

According to the experimental procedure as described in Example 54, the phantom -2- (6-fluoroimidazo[l,2-a]n ratio σ -3- -3- chen -3- base) was sprayed -4- The amine (Preparation 9b) was obtained as a white solid (59%) with 309 201130835 and 3,3,3-trifluoropropanoic acid by reverse phase chromatography (from Waters C-18 oxidized stone eve, water/1 : 1 acetonitrile· decyl alcohol as a dissolving agent [buffered with 0.1% v/v citric acid buffer] 0 〇 / 〇 to 1 〇〇 %). The crude product was purified. LRMS (m/z): 423 (M+l) +. -NMR δ (CDC13): 1.25 (s, 2H), 1.73 (bs, 2H), 1.90 (bs, 2H), 2.15 (bs, 2H), 3.42 (bs, 2H), 6.22 (d, 1H), 6.27 (d, 1H), 7.25 - 7.19 (m, 1H), 7.68 (td, 1H), 8.29 (t, 1H), 8.49 (s, 1H), 8.53 (s, 1H), 9.97 (s, 1H). 'Example 67 2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-indole_[(3 and)_1_(1 and _n-biazole-4-ylcarbonyl)piperidin-3-yl Pyrimidine-4-amine

According to the experimental procedure as described in Example 52, from (7^)-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-indole; piperidin-3-yl)pyrimidine- 4-Amine (Preparation 9b) and 10,000 more than β-s--4-carboxylic acid gave a solid (33%). Purification of the crude product by reverse phase chromatography (C-18 cerium oxide from Waters, water/1:1 acetonitrile-methanol as the eliminator [0% to 100% buffered with 0.1% ν/ν citric acid) . LRMS (m/z): 407 (M+l)+. H-NMR δ (CDC13): 2.65 (d, 4H), 3.21 - 3.24 (m, 2H), 310 201130835 3.50 (d, 2H), 3.79 (d, 2H), 6.27 (d, 1H), 7. GG (bs,1H) 7 7.29 (m,1H), 7.71 (dd,1H), 7.91 (s,1H), 8.28 (d, iH) 8 _ (s, 1H), 9.97 (dd, 1H) ), ·47 Example 68 (10) 'Cyanomethyl)_3_{[2_(6_Fluoro[]U2Exopyrimidin-4-yl]aminomethylpiperidin-j-carboxamide

According to the experimental procedure as described in Example 56, from (8)_2-[l,2-a]pyridin-3-yl)(piperidin-3-yl)-pyridin-4-amine (preparation %|,, and moth 1-((Cyanomethyl)(indenyl)amine-methylidene methyl hydrazine (Preparation 37b) gave a solid (33%) by reverse phase chromatography (C-European C-18 dioxide) Shi Xi, water / 1:1 B guess · methanol as the dissolving agent = 〇.1% v / v formic acid buffer] 〇% to loo%) purified crude product LRMS (m / z): 409 (M + l) + 'H-NMR δ (CDC13): 1.67 (bs, 1H), 1.83 (bs, 1H), 2.01 (bs, 1H), 2.26 (bs, 2H), 3.00 (s, 3H), 3.30 (bs, 1H) ), 3.44 (bs, 2H), 3.66 (bs, 1H), 3.96 - 4.17 (m, 2H), 5.75 (bs, 1H), 6.28 (bs, 1H), 7.18 - 7.32 (m, 1H), 7.71 ( Dd, 1H), 8.26 (bs5 1H), 8.50 (s, 1H), 10.00 (dd, 1H) 311 201130835 Example 69

NH added a concentrated aqueous solution of hydrogen chloride (10) 1 ml) to the disturbed (i?)-2-(3-(2_(6-fluoroimidazo(1)2♦ specific base) mouth bite ·4·ylamino group)贫 -1- -1- ) · · -1- -1- -1- -1- -1- ϋ 对 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Overnight. The reaction mixture was acidified and extracted with m. The organic phase was washed with a 4% carbon g line aqueous solution and brine. The aqueous phase was extracted with trichloromethane and dried (MgS04) combined organic phase 'evaporated and subjected to reverse phase chromatography (from Waters c_18 dioxide, water/1:1 acetonitrile-methanol as the dissolving agent) The residue was purified with EtOAc EtOAc (EtOAc:EtOAc LRMSv (m/z): 398 (M+l)+. ·- !H-NMR δ (CDC13): 1.15 (d, 6H), l.9〇 (bSj 4H), 2.01 - 2.14 (m, 2H), 2.28 - 2.45 (m, 2H), 2.74 (bs, 1H) ), 3.76 - 3.87 (m, 2H), 5.53 (bs, 1H), 6.20 (d, 1H), 7.27 (dd, 1H), 7.72 (dd, 312 201130835 1H), 8.26 (bs, 1H), 8.52 ( s, 1H), 10.01 (dd, 1H) Example 70 2-(6-fluoroimidazo[1,2·&lt;ι) oxaridin-3-yl)-7V-methyl•7V-[(3i?) -l-(3,3,3-di-propyl propyl) brigade-3-yl] pain bite-4-amine

According to the experimental procedure as described in Example 54, from (i?)-2-(6-fluoroimidazo[l,2-a]0 to -3-yl)-TV-fluorenyl (Brigade π- 3-yl) oxime-4-amine (preparation of lib) and 3,3,3-trifluoropropionic acid gave a white solid (83%). The crude product was purified by flash chromatography (0-5% methanol in dichloromethane). LRMS (m/z): 437 (M+l)+. ^-NMR δ (CDC13): 1.83 - 2.14 (m, 4H), 3.05 (s, 2H), 3.07 (s, 3H), 3.12 - 3.41 (m, 3H), 3.78 (bs, 2H), 6.36 (t , 1H), 7.24 (dd, 1H), 7.70 (dt, 1H), 8.30 - 8.40 (m, 1H), 8.53 (s, 1H), 9.91 (dd, 1H) Example 71 (Λ)-3-(3 -((2-(6-fluoroimidazo[l,2-a] acridine-3-yl)pyrimidin-4-yl)(methyl)amino)piperidin-1-yl)-3-sideoxy Propiononitrile 313 201130835

According to the experimental procedure as described in Example 46, from (Λ)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)-#-mercapto-indolyl-3-yl Pyrimidine-4-amine (preparation of lib) and 3-[(2,5-di- oxetyrridin-1-yl)oxy]-3-oxo-propanenitrile (as in BE 875054 (A1)) Preparation) A white solid (77%) was obtained. The crude product was purified by flash chromatography (0-5% methanol in dichloromethane). LRMS (m/z): 394 (M+l)+. H-NMR δ (CDC13): 1.71 - 2.14 (m, 4H), 2.57 - 2.68 (m, 1H), 2.80 (s, 3H), 3.06 (s, 2H), 3.13 - 3.35 (m, 2H), 3.71 -3.86 (m, 2H), 4.62 - 4.75 (m, 1H), 6.37 (dd, 1H), 7.24 (dt, 1H), 7.68 (dt, 1H), 8.31 - 8.40 (m, 1H), 8.54 ( s, 1H), 9.86 (dd, 1H) Example 72 (i?)-l-(3-((2_(6-fluoroimidazo[l,2-a]"pyridin-3-yl)pyrimidine-4 -yl)(methyl)amino)piperidin-1-carbonyl)cyclopropanecarbonitrile

314 201130835 according to the experimental procedure as described in Example 48, from (and)-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-#-methyl-piperidin-3 -yl)pyrimidine-4-amine (preparation of lib) and 1-cyanocyclopropanedecanoic acid gave a white solid (47 〇 / 〇). The crude product was purified by flash chromatography (0-8% methanol in dichloromethane) then EtOAc. LRMS (m/z): 420 (M+l)+. !H-NMR δ (CDC13): 1.55 (bs, 4H), 1.90 - 2.14 (m, 4H), 2.80 - 2.94 (m, 1H), 3.08 (s, 3H), 3.15 - 3.31 (m, 2H), 4.53 (d, 2H), 6.39 (bs, 1H), 7.23 (dd, 1H), 7.68 (dd, 1H), 8.33 (d, 1H), 8.51 (bs, 1H), 9.91 (bs, 1H) Example 73 3·((3Λ)·3-{ethyl[2-(6_象味唆 and [1,2-/|]吼-3-yl) bite _4_yl]amino}piperidine- 1-yl)-3-oxopropiononitrile

According to the experimental procedure as described in Example 46, ^^ethyl_2_(6_ 氟味嗤和[1,2-十比咬_3_基)|[(3外派咬_3_基Mouth bite glacial amine (preparation 12b) and 3_[(2,5-di-oxyl group such as chloro]1 yl)oxy]·3· pendant oxypropionitrile (prepared as described in ΒΕ_4 (Α1)) Obtained as a white solid 315, EtOAc, EtOAc (EtOAc: EtOAc: EtOAc) CDC13): 1.30 (bs, 3H), 1.77 (bs, 2H), 2.02 (bs, 2H), 2.84 (d, 1H), 3.18 (bs, 2H), 3.39 - 3.59 (m, 4H), 3.79 (bs , 1H), 4.72 (bs, 1H), 6.33 (bs, 1H), 7.23 (bs, 1H), 7.68 (bs, 1H), 8.32 (bs, 1H), 8.37 - 8.55 (m, 1H), 9.80 - 10.01 (m, 1H) Example 74 Ethyl-2-(6-fluoroimidazo[l,2-ii]pyridin-3-yl HV-[(3i?)-l-(3,3,3-trifluoro Propionyl) piperidin-3-yl]pyrimidine-4-amine

According to the experimental procedure as described in Example 54, from ethyl-2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-A4(3i?)-piperidin-3-yl] Pyrimidine-4-amine (Preparation 12b) and 3,3,3-trifluoropropionic acid gave a solid (52%). The crude product was purified by flash chromatography (92:8 dichloromethane / methanol). LRMS (m/z): 451 (M+l)+. ^-NMR δ (CDC13): 1.30 (t, 3H), 1.92-2.18 (m, 2H), 2.51 - 2.66 (m, 1H), 2.82 (bs, 1H), 3.14 (s, 2H), 3.19 - 3.28 (m, 1H), 3.32 (q, 2H), 3.51 (bs, 2H), 3.74 - 3.92 (m, 1H), 316 201130835 4.79 (t, 1H), 6.34 (d, 1H), 7.23 (d, 1H ), 7.68 (dt, 1H), 8.29 - 8.36 (m, 1H), 8.42 - 8.54 (m, 1H), 9.88 - 9.99 (m, 1H) Example 75 3_((3 and)_3_{(cyclopropylmethyl) )[2_(6·Fluorol odor is better than bite 3) Pyrimidine _4_yl]amino}} benzyl-1-yl)·3_sideoxypropionitrile

According to the experimental procedure as described in Example 46, from the base -2_(6_Fluorum π-salt[ι,2·α]η ratio bite_3·yl)|[(3 and)^ in the ring Dodamine (preparation 1:3b) and H (2,5-di- oxy group ^^^3·yl]pyridyl]·3·side oxypropionitrile (such as ΒΕ875〇54 (Α1)) Bite -1 '' base) aerochromatic solid (77%). The crude white product was obtained by flash chromatography (0-8% methanol). m.m. m. +l)+. ^-NMR δ (CDC13): 0.39 (bs, 2H), 〇6? (bs, 1H), 1.95 - 2.18 (m, 4H), 2.97 (bs, 3^2H), 2H), 321 (s, 2H ), 3.57 (s, 2H), 3.79 (bs, iH, "3, 36 (m, 1H), 6.48 (dd, 1H), 7.18 - 7.30 (m, 1H), 7 68 (eg (m, 8.38) (m, 1H), 8.51 (s, 1H), 9.92 (dd, 1H) 'lH), 8.27 - Example 76 317 201130835 A4 cyclopropylmethyl)-2-(6-fluoroimidazo[1,2-d Bubidine-3·yl)-7V-[(3i?)-l-(3,3,3-trifluoropropenyl)piperidin-3-yl]pyrimidin-4-amine

According to the experimental procedure as described in Example 54, from indole propylmethyl)-2-(6-fluoroimidazo[1,2-ίφ-pyridin-3-yl)-indole 4(3 and)-piperidine- 3-yl]pyrimidin-4-amine (Preparation 13b) and 3,3,3-trifluoropropanoic acid afforded white solid (75%). 'H-NMR δ (CDC13): 0.38 (d, 2H), 0.65 (d, 2H), 1.11 (bs, 1H), 1.46 (d, 2H), 1.92 - 2.19 (m, 2H), 2.92 (bs, 1H), 3.09 -3.28 (m, 3H), 3.47 (bs, 2H), 3.86 (bs, 1H), 4.72 - 4.91 (m, 2H), 6.47 (t, 1H), 7.24 (dd, 1H), 7.68 (dd, 1H), 8.27 - 8.38 (m, 1H), 8.51 (s, 1H), 9.97 (ddd, 1H) Example 77 3-((3i?)-3-{[5-fluoro-2-(6 -Fluoroimidazo[1,2-«]pyridin-3-yl)pyrimidin-4-yl]amino}Nanyl-1-yl)·ν3-side gas-based Cyan 318 201130835

According to the experimental procedure as described in Example 46, (/^)-5-fluoro-2-(6-fluoro-salt[lj-ahb11--3-yl)-7V-(唆唆-3-基) Mint-4-amine (preparation 17b) and 3-[(2,5-di-oxyxyrrolidin-1-yl)oxy]-3-oxo-propanenitrile (such as BE875054 (A1) The preparation) gave a white solid (67%). The crude product was purified by flash chromatography (0-8% EtOAc in dichloromethane). LRMS (m/z): 398 (M+l)+. !H-NMR δ (CDC13): 1.73 - 2.00 (m, 2H), 2.21 (bs, 2H), 3.29 - 3.39 (m, 1H), 3.45 (s, 2H), 3.48 - 3.68 (m, 2H), 4.24 -4.41 (m, 2H), 5.18 (bs, 1H), 7.68 (ddd, 1H), 8.16 (d, 1H), 8.40 (s, 1H), 8.51 (s, 1H), 9.80 - 9.91 (m, 1H) Example 78 5-Fluoro-2-(6-fluoroflavor [1,2-flf] n ratio bite_3_ base)-?V-[(3i?)-l-(3,3,3- Trifluoropropionyl)piperidin-3-yl]pyrimidine-4-amine

319 201130835 according to the experimental procedure as described in Example 54, by (Fantasy_5_fluoro-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-indole-(piperidinyl)pyrimidine_4 The amine (preparation 17b) and 3,3,3-trifluoropropanoic acid gave a white solid (yield: 63%). The crude product was purified by flash chromatography (0 </ </RTI> </RTI> <RTIgt; m/z): 441 (M+l)+. W-NMR δ (CDC13): 1.69 - 2.01 (m, 3H), 2 18 buckles, 1H), 3·16 - 3.27 (m, 1H), 3.19 - 3.46 (m, 2H), 3.48 (d, 1H), 3.54 . 3.65 (m, 1H), 3.89 - 4.23 (m, 1H), 4.26 - 4.37 (m, 1H), 5.04 . 5.27 (m, 1H), 7.25 (ddd, 1H), 7.69 (td, 1H), 8.16 (dd 1H) 8.37 - 8.54 (m,1H), 9.87 (ddd,1H) ' Example 79 3-((3J?)-3-{[2 -(6-rabbit "^ and [1,2_啦咬_3_基)5_交-4-yl]amino} ketone-1-yl)·3·sideoxypropionitrile

According to the experimental procedure as described in Example 46, from 2_(6·gas=, 2·3·yl)·5·methyl#_)食_3_基] Pei cut 20b) and 3-[(2 , 5-tertiary oxymethylene small group) (^ endonitrile (as prepared by deleting 75054 (A1)) = base (66%). by flash chromatography (〇_8% methanol two gas Methane ice liquid ^1 solid 320 201130835 crude product LRMS (m/z): 394 (M+l) + JH-NMR δ (CDC13): 1.82 (bs, 2H), 2.09 (bs, 5H), 3.40 ( (bs, 2H) , 7.67 (bs, 1H), 8.04 - 8.18 (m, 1H), 8.39 - 8.56 (m, 1H), 9.95 (d, 1H) Example 80 2_(6_ smell saliva [l,2-flf]n ratio Benzo-3-yl)-5-methyl-oxime (3 and)-l-(3,3,3-trifluoropropionyl)piperidin-3-yl-pyrimidin-4-amine

According to the experimental procedure as described in Example 54, from 2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-5-mercapto-TV-[(3i〇-piperidine-3) -yl]pyrimidin-4-amine (preparation 20b) and 3,3,3-trifluoropropanoic acid afforded a white solid (yield: 59%) eluted with flash chromatography (0-8% decyl alcohol in dichloromethane) The crude product was purified. LRMS (m/z): 437 (M+l) + lH-NMR^6 (CDC13): 1.68 (s, 3H), 1.77 (bs, 1H), 1.86 (bs, 2H), 2.07 (d, 2H), 2.19 (bs, 1H), 3.12 - 3.23 (m, 1H), 3.62 (bs, 1H), 3.74 - 3.94 (m, 2H), 4.39 (bs, 1H), 4.99 (d, 1H ), 7.16 - 7.26 (m, 1H), 7.62 - 7.73 (m, 1H), 8.11 (s, 1H), 321 201130835 8.41 - 2 (Γ, 出), 8.48 (s, 1H), 9.

tMSL 96 (bs,1H) Amino}pyrrolidiniumfluoroimidazo[1,2_&lt;1]pyridine-3-yl)pyrimidin-4-yl]-yl)-3-teranylpropiononitrile

According to the truth, you 丨 4 &lt; I and [1, 2♦ than the bite ^ described in the experimental procedure, from (4) - lead fluoride tastes to 艿-based from ten to each 0 _3_ base) mouth 0 toluidine (Preparation 21b) An oxyl-carbonitrile (prepared as described in (A1)) afforded a white solid (15 〇/〇). The crude product was purified by flash chromatography (9.1 hexanes / methanol). LRMS (m/z): 366 (M+l)+. ^-NMR δ (CDC13): 2.03 - 2.17 (m, 1H), 2.28 - 2.52 (m, 2H), 3.50 (s, 2H), 3.63 - 3.79 (m, 2H), 3.81 - 3.89 (m, 1H) , 3.95 - 4.02 (m, 1H), 6.26 (dd, 1H), 7.20 - 7.31 (m, 1H), 7.69 (ddd, 1H), 8.28 (d, 1H), 8.51 (d, 1H), 9.98 (dd , 1H) Example 82 3] 4-[4-(cyanoethenylhydrazine, 4·diazepane-i_yl]pyrimidine: yl}imidazo[l,2-tf]acridine-6 -carbonitrile 322 201130835

N according to the experimental procedure as described in Example 46, from 3-(4-(1,4-diazacycloheptan-1-yl)-2-yl)-salt and [small ratio _6 The carbonitrile (preparation 22b) and 3-[(2,5-di- oxy η is slightly succinyl)oxy»-oxypropanenitrile (prepared as described in ΒΕ 875054 (Α1)) give a white solid (5) %). By reverse phase chromatography (from Waters (: _18 cerium oxide, water / 1:1 acetonitrile • methanol as a dissolving agent [0.1% ν / ν acid buffer] 0% to 1%) The crude product was purified. LRMS (m/z): 387 (M+l) + 〇!H-NMR δ (CDC13): 1.22 - 1.40 (m, 2H), 3.41 (s, 2H), 3.46 - 3.58 (m, 2H), 3.60 (bs, 2H), 3.65 - 3.94 (m, 2H), 4.26 .4.38 (m, 2H), 6.41 (dd, 1H), 7.42 (ddd, 1H), 7.79 (dd, 1H), 8.35 (t, 1H), 8.55 (d, 1H), 10.55 (d, 1H) f Example 83 3-((3 and)-3-{[5·Ga-2-(6-fluoro miso[1, 2·ίΐ] "Bitter-3-yl" bite-4-yl]amino}piperidinyl)_3_sideoxypropionitrile

323 201130835 According to the experimental procedure as described in Example 46, '5-chloro-2-(6- Dunwei σ sits and [1,2_β]α is more than -3-3) 4-Amine (Preparation 43b) and 3-[(2,5-di-oxypyrrolidinyl)oxy].3,oxypropionitrile (prepared as described in ΒΕ875054 (Α1)) to give a solid ( 68%). The crude product was purified by flash chromatography (0-10% methanol in hexanes). LRMS (m/z): 414 (M+l)+. NMR δ (CDC13): ppm 1.71 - 2.03 (m, 2H), 2.20 (dd 1H), 3.29 3.52 (m, 2H), 3.57 (s, 2H), 3.59 - 3.70 (m, 1H): 3.80 - 3.94 ( m, 1H), 4.23 - 4.42 (m, 1H), 5.33 - 5.49 (m, lH)' 7.29 (dd, 1H), 7.73 (dd, 1 H), 8.27 (s, 1H), 8.56 (s, 1H ) 9 82 (dd, 1H). Example 84 3, ((10)-3_{[2_(6-Fluorim&lt;&[;[12] than _3 base) shouting _ amino} Niangbitin-1-yl)-2,2-dimethylpropane Nitrile

Mixing (8)_2-(6-fluoroimidazolium oxime pyridine-3-yl) 4-amine (0.45 g, M4 mmol, preparative base) 2-cyano-2-mercaptopropyl benzenesulfonate (〇 18 g, 〇72亳 曱 US US2007/299111A1 example 17b) and stirred at 125 °c c) from 324 201130835 The mixture was dissolved in ethyl acetate and washed with sodium hydroxide and hydrazine. Dry the organic layer and evaporate by reverse phase chromatography (washing erbium dioxide from Waters®, water/1:1 acetonitrile-methanol as the leaching agent [via 〇1% w c_18 buffer]0〇/〇 to 100 The resulting residue was purified to give the yt-carboxylic acid compound (3%). - Title of the title LRMS (m/z): 394 (M+l)+. ΐΗΝΜΚδ (CDCl3): 1.34 (s, 3H), l39 (bs, 4H), 2.39 - 2.53 (m, 2H), 2.6 () (bs, 2H), 2 s ' = 2.92 (bs, 1H), 5.67 ( Bs,1H), 6.24 (d,lH),7 2&lt;w ' ), 7.69 (dd, 1H), 8.21 (bs, 1H), 8.51 (s, 1H), l〇.〇〇( m 1H)» Complex 185, (10), iH). 2. Amine-based handsome gamma base

〇36 15 ethylamine (M9 ml), 2 also made of amine ϋ 亳 Moer) added dropwise to (Λ)_2·(6-fluoroimidazolium ketone)-Ν十辰唆_3_base) _4 • Amine (4) g, 〇3=, 卯) in a two-gas methane (5 liter) solution. The core is prepared at C'. The solvent was removed under reduced pressure and purified by mixing the second-distilled-dioxide-water-acetonitrile-:3⁄4 325 201130835 0.1% v/v citric acid buffer] 〇〇/〇 to 100 〇/〇) The title compound was obtained (jjjj: LRMS (m/z): 370 (M+l)+. NMR NMR δ (DMSO-J6): 1.46 (bs, 1H), 1.62 (bs, 1H), 1.71 - 1.89 (m, 2H), 2.36 (d, 2H), 2.83 (d, 1H), 3.17 (s, 2H), 4.28 (bs, 2H), 6.43 (d, 1H), 7.17 (bs, 1H), 7.37 (bs, 1H), 7.52 (ddd, 1H), 7.60 (d, 1H), 7.81 (dd, 1H) ), 8.29 (s, 1H), 8.40 (s, 1H), 9.97 (bs, 1H) ° ' Example 86 (5)-2-(6-fluoroimidazo[1,2-&lt;|] acridine- 3-yl)-ΛΓ·(1-(5-fluoropyridine-2-yl)ethyl) mouth bite-4-amine

克 '0.42 mmol, preparation), (8) small (5·!^pyridin-2-yl)ethylamine (66 mg '0.47 mmol, prepared as described in WO2006/82392) and diisopropyl The mixture of ethylamine (400 μL, 2.52 mmol) in THF (5 mL) was warmed to reflux until the reaction was completed. The solvent was evaporated under reduced pressure and the residue was partitioned between dit. The organic layer was separated and washed with water and brine, dried over sodium sulfate and solvent evaporated. Purification of the residue by reverse phase chromatography (from Waters CM8 Dioxide 326 201130835 矽, water / 1:1 acetonitrile-methanol as the eliminator [0.1% v/v citrate buffer] 0% to 100%) The title compound (58 mg, 39%) was obtained. LRMS (m/z): 353 (M+l)+. ]H NMR δ (CDC13): 1.66 (d, 3H), 5.15 - 5.44 (m, 1H), 5.98 (d, 1H), 6.24 (bs, 1H), 7.21 - 7.30 (m, 2H), 7.38 -7.45 (m, 2H), 7.71 (dd, 1H), 8.25 (d, 1H), 8.42 - 8.56 (m, 1H), 9.94 (d, 1H). Example 87 2-(6-Fluoroimidazo[l,2-fl]acridin-3-yl)-#decaderidin-2-ylmethyl)pyrimidine-4-amine

3-(4-Aluthiopyrimidin-2-yl)-6-fluoroimidazo[1,2-a]pyridine (43.7 mg, 0.18 mmol, Preparation 44), pyridine-2-, under argon atmosphere Base-decalamine (36 μl, 0.35 mmol), 2'-(dicyclohexylphosphino)-AUV-dimercaptobiphenyl-2-amine (10 mg, 0.03 mmol), ginseng Benzomethaneacetone) palladium (0) (13 mg, 0.01 mmol) and sodium tributoxide (24 mg, 0.25 mmol) of toluene (5 mL) were heated to 110 ° C overnight. The solvent was removed under reduced pressure and subjected to reverse phase chromatography (C-18 from Waters, water/1:1 acetonitrile-methanol as the dissolving agent [buffered with 0.1% v/v citric acid 327 201130835] The residue was purified to give the title compound (m. LRMS (m/z): 321 (M+l)+. NMR NMR δ (CDC13): 4.80 (bs, 2H), 6.23 (bs, 1H), 6.32 (d, 1H), 7.14 - 7.29 (m, 3H), 7.40 (d, 1H), 7.70 (ddd, 1H) , 8.26 (d, 1H), 8.54 (s, 1H), 8.61 (d, 1H), 9.96 (dd, 1H) 〇 Example 88 (5)-2-(6-fluoroimidazo[l,2-a] &quot;Bistidin-3-yl)-Λ4Η4-fluorophenyl) butyl)pyrimidine-4-amine

According to the experimental procedure as described in Example 87, from 3-(4-azepine)-6-fluoroimidazo[l,2-a]pyridine (50 mg '0.2 mmol, Preparation 44) and (3) 1-(4-Fluorophenyl)butan-1-amine (49 mg, 0.24 mmol, as described in Tetrahedron: Asymmetry 2001, 12 (15), 2185-2190) afforded a white solid (37%) . LRMS (m/z): 380 (M+l)+. 4 'H NMR δ (CDC13): 0.98 (t, 3 Η), 1.31 - 1.53 (m, .2H), 1.72 - 2.04 (m, 2H), 4.82 (bs, 1H), 5.15 5.39 (m, 1H), 6.09 (bs, 1H), 7.04 (t, 2H), 7.22 (ddd, 1H), 7.34 (dd, 2H) 328 201130835 7.66 (dd, 1H), 8.20 (d, 1H), 8.49 (s, 1H), 9.86 (bs, 1H). Example 89 〇R)-3_(2_(6-fluoroimidazo[1,2-ύτbbidin-3-yl)pyrimidin-4-ylamino)--1-propyl**

According to the experimental procedure as described in Preparation 5a, from 2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-ol (122 mg, 0.53 mmol, Preparation 8b) And (phantom-3-amino-1-propylpyrrolidin-2-one (170 mg, 0.63 mmol, prepared as described in J. Med. Chem. 1999, 42(18), 3557) obtained white Solid (5%) LRMS(m/z): 355 (M+l) + NMR δ (CDC13): 0.95 (t,3Η), 1.77 - 1.37 (m, 2H), 2.18 - 1.77 (m, 2H ), 3.67 - 3.21 (m, 4H), 5.82 - 5.75 (m, 1H), 6.33 (d, 1H), 7.37 - 7.16 (m, 1H), 7.74 (dd, 1H), 8.24 (t, 2H), 8.48 (d, 1H), 10.01 (d, 1H). Example 90 6-Fluoro-3-(4·(2-(pyridin-2-yl)pyrrolidin-1-yl)pyrimidin-2-yl)imidazole [1,2-α]π ratio bite 329 201130835

Prepare 8b according to the experimental procedure as described in Preparation 5a from 2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ol (100 mg, 0.43 mmol) And 2-(pyrrolidin-2-yl)pyridine (129 mg, 0.87 mmol) gave a white solid (22%). LRMS (m/z): 361 (M+l)+. !H NMR δ (CDC13): 1.99 - 2.36 (m, 6H), 2.42 - 2.73 (m, 2H), 3.45 - 3.90 (m, 2H), 3.92 - 4.29 (m, 2H), 4.99 (bs, 2H) , 5.55 (bs, 1H), 5.89 (bs, 1 H), 6.33 (bs, 1H), 7.05 - 7.23 (m, 4H), 7.51 - 7.76 (m, 4H), 8.01 - 8.40 (m, 4H), 8.52 (s, 1H), 8.63 (d, 2H), 9.34 (bs, 1H), 9.92 - 10.19 (m, 1H). Example 91 (5HV,7V·diethyl-1-(2-(6-fluoroimidazo[l,2-fl]pyridin-3-yl)pyrimidin-4-yl)pyrrolidine-2-carboxamide

330 201130835 Adding six gas-filled α (7-azapine in urine (46 mg, millimolar, 0.12 mmol) Adding a butterfly: propylethylamine (22 -3-yl) to -4 Boat to the ground: two preparations 45b) of dimethylformamide (.12 millimoles 'after the minute' added diethylamine (16 micro's liquid. Stir 30, 10 microliters, 0.14 millimolar, The Japanese and Tian Ding stirred the reaction for another 3 hours. It was hot, such as a pen, and it was smashed to the right. It was separated from the right, the water, and the residue was distributed to the water. Remove the organic layer from the chlorine, wash the strip with water and brine, dry over sodium sulfate and evaporate the solvent by reverse phase chromatography (from Waters C-18 Semenite, water / 1:1) The title compound (17 mg, 37%) was obtainedjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj M+) NMR δ (CDC13): 1.10 (t, 3Η), 1.39 (t, 3Η), 1.66 (bs, 2H), 2.09 (ddd, 2H), 2.27 - 2.41 (m, 2H), 3.30 - 3.64 ( m, 2H), 3.65 - 3.84 (m, 2H), 5.10 (bs, 1H), 6.29 (d, 1H), 7.20 (ddd, 1H), 7.63 (dd, 1 H), 8.27 (d, 1H), 8.34 (bs, 1H), 9.93 (bs, 1H). Example 92 (and) _Α^ν-diethyl-1-(2-(6-fluoroimidazo[1] ,2·β]pyridin-3-yl)acridin-4-yl)pyrrolidine-2-carboxamide 331 201130835

According to the experimental procedure as described in Example 91, from (7?)-l-(2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidin-4-yl)pyrrolidine- 2-decanoic acid (40 mg, 0.12 mmol, Preparation 46b) and diethylamine (15 <RTIgt; LRMS (m/z): 382 (M+). !H NMR δ (CDC13): 1.10 (t, 3H), 1.39 (t, 3H), 1.99 - 2.16 (m, 2H), 2.26 - 2.41 (m, 2H), 3.29 - 3.63 (m, 5H), 3.67 -3.85 (m, 1H), 5.09 (bs, 1H), 6.28 (bs, 1H), 7.20 (dd, 1H), 7·63 (dd, 1H), 8.28 (d, 1H), 8.35 (bs, 1H) ), 9.93 (bs, 1H). Example 93 2-((lr,4r)-4-(2-(6-Fluorobenzo[l,2-ii]0-biti-3-yl) Pain-4-ylamino)cyclohexyl) Acetonitrile

Prepared by 3-(4-chloropyrimidin-2-yl)-6-fluoroimidazo[l,2-a]acridine (90 mg, 0.36 mmol) according to the procedure of procedure 201130835 44) and 2-((7#)-ylaminocyclohexyl)acetonitrile (5 </RTI> <RTIgt; </RTI> <RTIgt; LRMS (m/z): 351 (M+l)+. H-NMR5 (CDCl3): 0.8 (m, 4H), l22_138 (m (m, 1H), 2.0 (m, 1H), 2.3 (d, 2H), 4.9 (bs, 1H), 6.2 (dm; 8 7 ^(m, !H), 7.7 (dd, 1H), S.2 Example 94 (Λ)-2-(3-(2-(6-1)pyrano[i,2_yl)piperidin-1- Acetonitrile

a] pyridin-3-yl)pyrimidine _4•ylamine at room temperature will be (8)-2_(6_L sit and [u♦ than bite _3 bit-3-yl) mouth bite 4-amine (13 〇, 0.42 亳 Mo Er, Preparation &quot; 十底基甲气 (58 mg, 〇·42 mmol, as prepared in Side (4) 3) and triethylamine (58 μL, 0.42 mmol 2 = ML) When the solution is satisfactory, the reaction mixture is diluted with water and the mixture is washed with 4% aqueous sodium hydrogencarbonate solution, dried over sulphur, filtered and evaporated under reduced pressure. The title compound (5) was obtained by chromatography (from C. </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> <RTIgt; 333 201130835 mg, 3%) LRMS (m/z): 416 (M+l), '2.16 (m, 6H), 2.86 (m, iH), 6.36 (bs, 1H), 7.32 - 7.95 - 8.23 ( m, 1H), 8.47 !H NMR δ (CD3OD): 1.42 2H), 3,67 (m, 2H), 3.88 - 4.34 (m, 7.54 (m, 1H), 7.58 - 7.77 (m, 2H), ( Bs, 1H), 9.97 (bs, 1H). Example 95

W曱-mermorpholine (107 mg, 〇_96 mmol), hydrazine (3 dimethylaminopropyl)-AT-ethyl carbodiimide hydrochloride (92 mg, 〇 millimol), 1·Hydroxybenzotriazine (65 mg, 〇·48 mmol) to 、, _fluoroimidazo[l,2_a]pyridin-3-yl)-Ν-0-endridyl) guanidinylamine (3 〇克' 〇.1 millimolar 'preparation %) was added to 4,4,4_trimethylbutyric acid (27 mg, 〇.19 mmol), Ν-dimercaptoacetamide (1 ml) ) in solution. After stirring the mixture overnight, the solvent was removed under vacuum in a DD-4 apparatus. The residue was dissolved in ethyl acetate. EtOAc (EtOAc)EtOAc. The crude product was purified by EtOAc EtOAc (EtOAc) LRMS (m/z): 437 (M+l)+. !H NMR δ (CDC13): 1.83 (bs, 2H), 2.34 - 2.74 (m, 6H), 3.18 - 3.43 (m, 2H), 3.54 - 4.40 (m, 3 H), 5.17 (bs, 1H), 6.21 (d, 1H), 7.21 (t, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.51 (bs, 1H), 9.94 (d, 1H). Example 96 ((U)-3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-ylphenylcyclopropane Ketone

According to the experimental procedure as described in Example 95, from (7&amp;2π)-2-phenylcyclopropanecarboxylic acid (31 mg, 0.19 mmol) and (7))-2-(6-fluoroimidazo[1,2 -a]n ratio -3-yl)-7V-(Brunken-3-yl) oxime-4-amine (30 mg '0.1 mmol, Preparation 9b) gave a white solid (20 mg, 45%) ). LRMS (m/z): 457 (M+l)+. !H NMR δ (CD3OD): 0.96 - 1.08 (m, 1H), 1.25 -1.36 (m, 1H), 1.53 (d, 1H), 1.64 - 1.74 (m, 2H), 1.75 - 1.84 (m, 1H) , 1.90 (bs, 1H), 2.02 - 2.08 (m, 1H), 2.11 - 2.28 (m, 2H), 2.30 - 2.48 (m, 1H), 3.38 - 3.90 (m, 1H), 4.01 - 4.24 (m, 335 201130835 2H), 6.30 (d, 1H), 6.59 (bs, 2H), 6.72 - 6.81 (m, 2H), 7.20 (m, 1H), 7.28 (m, 1H), 7.42 - 7.55 (m, 1H) , 7.64 - 7.79 (m, 1H), 7.93 - 8.23 (m, 1H), 8.36 (s, 1H). Example 97 (Λ)-1-((1?)-3-(2-(6-fluoroimidazo[l,2-a]oxa-3-yl)pyrimidin-4-ylamino) ketone) -2-carbyl-3,3-dimethylbutan-1-indole

According to the experimental procedure as described in Example 95, from (/0-2-hydroxy-3,3-dimethylbutyric acid (25 mg, 0.19 mmol) and (7^)-2-(6-fluoro) Imidazo[l,2-a]n is more than -3-yl)-oxime "-(Big alpha-3-yl) gnat-4-amine (30 mg '0.1 mmol, preparation 9b) to obtain white Solid (32 mg, 78%). LRMS (m/z): 427 (M+l) +. *H NMR δ (CD3OD): 0.98 (s, 9H), 1.57 - 1.97 (m, 4H), 2.09 - 2.30 (m, 1H), 2.69 - 2.80 (m, 1H), 3.20 (d, 1H), 4.01 - 4.12 (m, 1H), 4.34 (s, 1H), 4.84 (s, 2H), 6.43 (d, 1H), 7.37 - 7.52 (m, 1H), 7.68 (dd, 1H), 8.09 - 8.22 (m, 1H), 8.41 (s, 1H), 8.51 - 8.59 (m, 1H), 10.02 (bs, 1H) Example 98 (Indole)-2-cyclopentyl-1-(3-(2-(6-fluoroimidazo[l,2-a]&quot;bipyridin-3-yl)pyridin-4-ylamine基)旅唆-1-基)乙嗣336 201130835

According to the experimental procedure as described in Example 95, 2-cyclopentylacetic acid (24 μL, 0.19 mmol) and (and)-2-(6-fluoroimidazo[l,2-a]pyridine- 3-Methyl)-AK piperidin-3-ylpyrimidin-4-amine oxime 0 mg, 0.1 mmol, mp. LRMS (m/z): 423 (M+l)+. ]H NMR δ (CD3OD): 0.94 (bs, 1H), 1.14 - 1.28 (m, 1H), 1.32 - 1.49 (m, 2H), 1.50 - 1.75 (m, 6H), 1.78 - 1.99 (m, 3H) , 2.04 - 2.33 (m, 2H), 2.46 (d, 1H), 2.84 (dd, 1H), 3.26 (dd, 1H), 3.42 (dd, 1H), 3.91 (d, 1H), 6.42 (d, 1H ), 7.45 (ddd, 1H), 7.70 (td, 1H), 8.18 (d, 1H), 8.41 (s, 1 H), 8.46 (s, 1H), 10.02 (d, 1H). Example 99 (i?)_l-(2-(3-(2-(6- odor salino[l,2_a]n is more than -3-yl) shouting 4-ylamino)piperidin-1- Base)-2-oxoethyl)-5-methylpyrimidine-2,4(1Η,3Η)-dione 337 201130835

According to the experimental procedure as described in Example 95, 2-(5-methyl-2,4-di-oxy-3,4-dihydropyrimidin-1(2//)-yl)acetic acid (35 mg, 0.19 millimolar) and (and)-2-(6-fluoro-[sodium]-[s, 2-a]u-bit each base) each (biting _3_ group) pyrimidine-4-amine (30 mg' 0.1 mmol, %% was obtained as a white solid (21 mg, 45%). LRMS (m/z): 479 (M+l)+. 1H NMR δ (CD3OD): 1.52 - 1.83 (m, 4H), 1.87 (d, 3H), 1.94 - 2.03 (m, 2H), 2.08 - 2.26 (m, 1H), 2.91 - 3.07 (m, 1H), 3.35 - 3.48 (m, 2H), 3.68 - 4.02 (m, 2H), 4.42 - 4.77 (m, 1H), 6.31 - 6.54 (m, 1H), 7.18 - 7.33 (m, 1H), 7.37 - 7.51 (m , 1H), 7.68 (dt, 1H), 8.07 - 8.26 (m, 1H), 8.46 (d, 1H), 10.05 (bs, 1H). Example 100 (i?)-l-(3-(2_(6-fluoroimidazo[l,2-a]«pyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl) -2-(1 from 1,2,4-triazol-1-yl)ethanone

338 201130835 According to the experimental procedure as described in Example 95, from 2-(7//-1,2,4-triazol-1-yl)acetic acid (24 mg, 0.19 mmol) and (7?)- 2-(6-fluoroimidazo[1,2-&amp;]° 唆-3-yl)-Λ"-(Big -3-yl) mouth bite-4-amine (30 mg, 0.1 mmol) , Preparation %) Obtained as a white solid (10 mg, 25%). LRMS (m/z): 422 (M+1). .H NMR δ (CD3OD): 1.76 (ddd, 3H), 1.84 - 2.03 (m , 2H), 2.18 (dd, 1H), 2.94 (dd, 1H), 3.80 - 4.06 (m, 2H), 4.56 (bs, 1H), 5.35 (d, 1H), 6.37 (d, 1H), 6.47 ( d, 1H), 7.34 - 7.52 (m, 1H), 7.67 (ddd, 1H), 7.94 - 8.03 (m, 1H), 8.09 - 8.25 (m, 1H), 8.44 (m, 2H), 10.04 (bs, 1H). Example 101 (i?)-(3_(2-(6-fluoroimidazo[l,2_a] aridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl) (1) -methylcyclohexyl)methanone

According to the experimental procedure as described in Example 95, 1-mercaptocyclohexane decanoic acid (27 mg, 0.19 mmol) and (Λ)-2-(6-fluoroimidazo[1,2-a] Bite-3-yl)-#-(^^-3-yl) oxime-4-amine (30 mg, 0.1 mmol, Preparation 9b) gave white solid (13 mg, 31%). LRMS (m/z): 437 (M+l)+. 339 201130835 ]H NMR δ (CD3OD): 1.25 (s, 3H), 1.30 - 1.57 (m, 9H), 1.58 - 1.71 (m, 2H), 1.83 - 1.95 (m, 1H), 2.04 (d, 2H) , 2.20 (s, 1H), 2.80 - 2.95 (m, 1H), 3.03 - 3.18 (m, 1H), 4.13 (bs, 1H), 4.23 (d, 1H), 4.52 (d, 1H), 6.38 (bs , 1H), 7.45 (ddd, 1H), 7.69 (dd, 1H), 8.15 (bs, 1H), 8.43 (s, 1 H), 10.02 (bs, 1H). Example 102 (2,2-Difluorocyclopropyl)((i?)-3-(2-(6.fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamine Piperidin-1-yl)methanone

According to the experimental procedure as described in Example 95, from 2,2-difluorocyclopropanecarboxylic acid (23 mg, 0.19 mmol) and (and)-2-(6-fluoroimidazo[1,2-a] </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; ): 417 (M+l)+.]H NMR δ (CD3OD): 1.48 - 1.85 (m, 4H), 1.85 -2.06 (m, 3H), 2.10 - 2.28 (m, 2H), 2.79 - 3.09 (m , 1H), 3.93 -4.10 (m, 2H), 6.31 - 6.49 (m, 1H), 7.46 (m, 1H), 7.70 (m, 1H), 8.19 (m, 1H), 8.41 (d, 1H), 8.45 - 8.52 (m, 1H), 10.04 (bs, 1H) 〇 340 201130835 Example 103 ((and)-3-(2-(6- scent and [l,2-a]β ratio -3-yl) ) 咬-4-ylamino)piperidin-1-yl)((/foot 25&gt; 2-hydroxycyclopentyl)methanone

According to the experimental procedure as described in Example 95, (1 ft 25 &gt; 2-hydroxycyclopentanecarboxylic acid (25 mg, 0.19 mmol) and (??)-2-(6-fluoroimidazolyl)- Λ - - - - 胺 胺 胺 胺 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( M+l)+. lU NMR δ (CD3OD): 1.50 - 1.99 (m, 8H), 2.15 (s, 2H), 2.79 - 3.04 (m, 1H), 3.06 - 3.15 (m, 1H), 3.41 - 3.53 (m, 1H), 3.75 - 3.86 (m, 1H), 3.89 - 4.29 (m, 1H), 4.31 - 4.49 (m, 1H), 4.65 (d, 1H), 4.59 - 4.69 (m, 1H), 6.42 (d, 1H), 7.34 -7.57 (m, 1H), 7.61 - 7.79 (m, 1H), 8.04 - 8.26 (m, 1H), 8.32 -8.55 (m, 2H), 10.02 (bs, 1H). 104 (^)-1-(3-(2-(6-fluoroimidazo[l,2-ap-pyridin-3-yl)pyrimidin-4-ylamino)) _1_基比嗤-1 -基)乙嗣341 201130835

According to the experimental procedure as described in Example 95, 2-(1//-pyrazol-1-yl)acetic acid (24 mg, 0.19 mmol) and (7^)-2-(6-fluoroimidazolium) [1,2-a] π is more than -3-yl)-7V-(b.sup.3-yl-3-yl)amine (30 oz, 0.1 mmol, %) obtained as a white solid (25.5 mg, 63% ). LRMS (m/z): 421 (M+1). *H NMR δ (CD3OD): 1.59 - 1.97 (m, 4H), 2.18 (bs, 2H), 3.02 (t, 1H), 3.84 (d, 1H), 3.98 (d, 1H), 4.48 (d, 1H ), 4.97 - 5.17 (m, 2H), 6.33 (t, 1H), 6.35 - 6.54 (m, 1H), 7.35 -7.60 (m, 2H), 7.62 - 7.74 (m, 2H), 8.07 - 8.26 (m , 1H), 8.38 - 8.50 (m, 1H), 10.05 (bs, 1H). Example 105 (Λ)-cyclohexyl (3-(2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)indanone

According to the experimental procedure as described in Example 95, from cyclohexanoic acid (25 ml 342 201130835 g, 0.19 mmol) and (i?)-2-(6-fluoroimidazo[1,2-a]« ratio Pyridin-3-yl)-AK piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 423 (M+l)+. !H NMR δ (CD3OD): 1.23 - 2.01 (m, 7H), 2.07 -2.25 (m, 2H), 2.40 (t, 1H), 2.63 - 2.73 (m, 1H), 2.78 (t, 1H), 3.21 (m, 1H), 3.40 (m, 1H), 3.56 - 3.66 (m, 1H), 3.79 (d, 1H), 3.83 - 3.99 (m, 2H), 4.15 (bs, 1H), 4.65 (d, 1H ), 6.43 (d, 1H), 7.47 (t, 1H), 7.63 - 7.76 (m, 2H), 8.09 - 8.26 (m, 1H), 8.37 - 8.51 (m, 1H), 10.02 (bs, 1H). Example 106 (/^)-(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl) (4 -mercapto-1,2,3-thiadiazol-5-yl)methanone

According to the experimental procedure as described in Example 95, 4-methyl-1,2,3-thiadiazol-5-decanoic acid (28 mg, 0.19 mmol) and (π)-2-(6- Fluoridino[l,2-a]^^-3-yl)-7V-(a benzo-3-yl) aceton-4-amine (30 mg, 0.1 mmol, % prepared) obtained white Solid (26.8 mg, 63%). LRMS (m/z): 439 (M+l)+. !H NMR δ (CD3OD): 1.57 - 2.27 (m, 8H), 2.51 (s, 343 201130835 3H), 2.73 (s, 3H), 3.13 (m, 2H), 3.25 (m, 2H), 3.36 - 3.62 (m, 2H), 4.03 (m, 2H), 4.18 (m, 2H), 6.41 (bs, 2H), 7.37 - 7.51 (m, 2H), 7.69 (dd, 2H), 8.16 (bs, 5H), 8.52 (bs, 1H), 9.85 (bs, 1H), 10.04 (bs, 1H). Example 107 (Λ)-1-(3_(2-(6-fluoroimidazo[l,2-a]n-pyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)- 2-(4-(hydroxymethyl)phenyl)ethanone

According to the experimental procedure as described in Example 95, 2-(4-(hydroxyindenyl)phenyl)acetic acid (32 mg, 0.19 mmol) and (and)-2-(6-fluoroimidazo[1] ,2-&amp;]'° ratio to 11--3-yl)-^-(〇辰.定-3-基) Mouth 0-1,4-amine (3〇家克,〇.1 mmol, preparation 9b) Obtained as a white solid (14.5 mg, 33%). LRMS (m/z): 461 (M+l)+. *H NMR δ (CD3OD): 1.46 (m, 1H), 1.65 (m, 2H), 1.87 (m, 1H), 2.10 (m, 1H), 2.86 (dd, 1H), 3.17 (t, 1H), 3.83 (s, 2H), 3.83 - 3.91 (m, 1H), 4.33 (bs, 1H), 4.59 (s, 2H), 4.63 (d, 1H), 6.37 (bs, 1H), 7.02 (bs, 2H) , 7.24 - 7.31 (m, 2H), 7.31 - 7.38 (m, 2H), 7.46 (dd, 1H), 7.70 (td, 1H), 8.14 (d, 1H), 8.36-8.51 (m, 2H), 9.93 (bs, 1H), 10.03 (bs, 1H). Example 108 344 201130835 ((and)-3-(2-(6- odor vomit [l,2-a]β ratio -3-yl) mouth bite ^ 4-aminol) brigade bite __ base )_3_phenylbutene-1-pyrene

According to the experimental procedure as described in Example 95, 〇S)-3-phenylbutyric acid (29 μl, 0.19 mmol) and ( Magic-2-(6-fluoroimidazo[1,2-a] Pyridin-3-yl)-#-(piperidin-3-yl)pyrimidin-4-amine (30 mg, 0.1 mmol, Preparation 9b) afforded a white solid (9 mg, 5%). z): 459 (M+l)+.H NMR δ (CD3OD): 1.11 (d, 3H), 1.34 (d, 3H), 1.48 - 1.96 (m, 8H), 2.06 - 2.23 (m, 4H) , 2.25 - 2.43 (m, 1H), 2.47 - 2.57 (m, 1H), 2.60 - 2.68 (m, 1H), 2.71 - 2.85 (m, 2H), 2.98 (d, 1H), 3.05 - 3.15 (m, 1H), 3.19 - 3.28 (m, 1H), 3.65 -3.76 (m, 2H), 3.79 (d, 1H), 4.56 (bs, 1H), 6.35 (d, 1H), 6.42 (d, 2H), 7.17 (td, 1H), 7.24 - 7.29 (m, 6H), 7.45 (qd, 2H), 7.66 (dd, 2H), 8.14 (bs, 1H), 8.18 (d, 2H), 8.38 (s, 2H), 8.46 (s, 1H), 9.94 (bs, 2H), 10.03 (bs, 1H). Example 109 (/?)_1·((Λ)·3-(2·(6-fluoroimidazo[1,2- a] acridine-3-yl)pyrimidine _4_ylamino) brigade)-3-phenylbutan-1-嗣345 201130835

According to the experimental procedure as described in Example 95, (and)-3-phenylbutyric acid (32 mg, 0.19 mmol) and (and)-2-(6-fluoroimidazo[1,2-a Acridine-3-yl)-7V-(piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 459 (M+l)+. NMR δ (CD3OD): 1.11 (d, 3Η), 1.34 (d, 3Η), 1.52 _ 1.78 (m, 8H), 1.81 _ 1.92 (m, 1H), 1.99 - 2.09 (m, 1H), 2.09 - 2.16 (m, 1H), 2.36 - 2.47 (m, 1H), 2.60 (ddd, 2H), 2.74 (d, 1H), 2.76 - 2.84 (m, 1H), 2.98 - 3.08 (m, 1H), 3.09 - 3.25 (m, 3H), 3.77 (d, 1H), 3.87 - 4.00 (m, 3H), 4.59 (d, 1H), 6.34 (d, 1H), 6.39 (d, 1H), 6.79 - 6.88 (m, 2H ), 6.88 - 6.96 (m, 4H), 7.19 (t, 1H), 7.26 - 7.34 (m, 4H), 7.41 - 7.51 (m, 2H), 7.70 (dd, 2H), 8.16 (d, 2H), 8.38 (s, 1H), 8.49 (s, 1H), 9.94 -10.00 (m, 1H), 10.01 - 10.07 (m, 1H). Example 110 (Λ)_1·(3·(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino) brigade bite-1_yl)-3 -(4-methoxyphenyl)propan-1-嗣346 201130835

According to the experimental procedure as described in Example 95, from 3-(4-decyloxyphenyl)propionic acid (35 mg, 0.19 mmol) and (i?)-2-(6-fluoroimidazo[1] , 2-a]pyridin-3-yl)-piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 475 (M+l)+. lR NMR δ (CD3OD): 1.37 - 1.97 (m, 8H), 2.06 -2.20 (m, 2H), 2.43 - 2.59 (m, 3H), 2.66 - 2.84 (m, 4H), 2.86 -2.95 (m, 2H) ), 3.06 - 3.17 (m, 1H), 3.41 (bs, 1H), 3.54 (s, 3H), 3.75 (s, 3H), 3.77 - 3.92 (m, 4H), 4.65 (d, 1H), 6.39 ( d, 6H), 6.76 (d, 1H), 6.79 - 6.87 (m, 4H), 7.19 (t, 1H), 7.37 - 7.52 (m, 2H), 7.66 (td, 2H), 8.15 (d, 2H) , 8.35 (s, 1H), 8.50 (s, 1H), 9.90 - 9.99 (m, 1H), 9.99 - 10.07 (m, 1H). Example 111 (i?)-(5-Fluoro-2,6-dihydroxypyrimidin-4-yl)(3-(2-(6-fluoroimidazo[l,2-a]0-biti-3-yl) ) 啸 -4--4-ylamino) trace bit-1-yl) formazan

347 201130835 according to the experimental procedure as described in Example 95, from 5-fluoro-2,6-dihydroxypyrimidine-4-furic acid (33 mg, 0.19 mmol) and (i?)-2-(6- Flutimidazo[l,2-a]pyridin-3-yl)-A4piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. %). LRMS (m/z): 469 (M+l)+. H NMR δ (CD3OD): 1.69 - 1.82 (m, 1H), 1.88 -2.07 (m, 3H), 2.11 - 2.28 (m, 1H), 2.98 (m, 1H), 3.66 (m, 1H), 3.79 (m, 1H), 4.10 (m, 1H), 6.43 (d, 1H), 7.42 - 7.54 (m, 1H), 7.71 (dd, 1H), 8.17 (d, 1H), 8.22 (d, 1H), 8.35 (s, 1H), 8.58 (bs, 1H), 10.02 (bs, 1H), 10.07 (bs, 1H). Example 112 (Λ)-2-(3-Phenylphenyl)-1-((and)_3-(2-(6-fluoroimidazo[l,2-a]&quot;bipyridin-3-yl)°3⁄4唆-4-ylamino) 唆-1-yl)-2-ylamino

According to the experimental procedure as described in Example 95, (i?)-2-(3-chlorophenyl)-2-hydroxyacetic acid (36 mg, 0.19 mmol) and (i?)-2-(6) -Fluorimidin π sit and [1,2-&amp;]° than white -3- base (bit -3- base) mouth bite 4-amine (30 oz, 0.1 mmol, % prepared) to obtain white Solid (9 mg, 20%). LRMS (m/z): 481 (M+l) + 348 s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s - 2.20 (m, 4H), 2.79 - 2.95 (m, 2H), 3.02 - 3.22 (m, 4H), 3.70 - 3.83 (m, 2H), 3.98 - 4.17 (m, 3H), 4.64 - 4.76 (m, 1H), 5.40 (s, 1H), 5.47 (s, 1H), 6.38 (bs, 1H), 6.85 - 7.25 (m, 2H), 7.34 - 7.42 (m, 4H), 7.42 - 7.54 (m, 3H) , 7.65 - 7.78 (m, 2H), 8.01 - 8.22 (m, 2H), 8.46 (s, 1H), 8.52 (s, 1H), 9.92 (bs, 1H), 10.02 (bs, 1H). Example 113 ( i?)-(3-(2-(6-fluoroimidazo[l,2-a]n-pyridin-3-yl)pyrimidin-4-ylamino)) 5* base) hyperthyroidism

Purified by pyrimidine-5-decanoic acid (24 mg, 0.19 mmol) and (phantom-2-(6-fluoroimidazo[l,2-a]acridin-3 according to the experimental procedure as described in Example 95. - AK-piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 419 (M+1). !H NMR δ (CD3OD): 1.68 - 1.81 (m, 3H) 1.83 - 1.97 (m, 2H) 2.00 - 2.27 (m, 3H) 3.02 (d, 2H) 3.48 (m, 2H) 3.66 (d, 2H) 3.93 - 4.25 (m, 4H) 6.41 (bs, 2H) 7.46 (t, 2H) 7.69 (bs, 2H) 7.95 - 8.25 (m, 4H) 8.52 (bs, 1H) 8.61 (bs, 4H) 8.91 349 201130835 ( s, 2H) 9.26 (s, 1H) 9.84 (bs, 1H) 10.06 (bs, 1H) Example 114 (i?)_(3-(2-(6-fluoroimidazo[l,2-a] acridine 3-yl)pyrimidin-4-ylamino)piperidin-1-yl)(1-(trifluoromethyl)cyclobutyl)methanone

According to the experimental procedure as described in Example 95, from 1-(trifluoromethyl)cyclobutanecarboxylic acid (32 mg, 0.19 mmol) and (i 〇-2-(6-fluoroimidazo[1,2] -a]a is a white solid (23 mg, 51%) as a white solid (23 mg, mp.). m/z): 463 (M+l)+. !H NMR δ (CD3OD): 1.60 - 1.80 (m, 3Η), 1.90 (m, 3H), 2.01 - 2.16 (m, 1H), 2.17 - 2.25 ( m, 1H), 2.31 - 2·44 (m, 1H), 2.45 - 2.62 (m, 2H), 2.67 - 2.96 (m, 2H), 3.08 - 3.21 (m, 1H), 3.55 - 3.79 (m, 1H) ), 6.39 (d, 1H), 7.46 (ddd, 1H), 7.70 (dd, 1H), 8.17 (bs, 1H), 8.40 (bs, 1H), 8.49 (bs, 1H), 9.91 -10.13 (m, 1H). Example 115 (Λ)-(3-(2-(6-fluoroimidazo[l,2-a]n-pyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl )(1-hydroxycyclopropyl)methanone 350 201130835

According to the experimental procedure as described in Example 95, 1-hydroxycyclopropanecarboxylic acid (20 mg, 0.19 mmol) and (/?)-2-(6-fluoroimidazo[l,2-a]pyridine- 3-yl)-AM;piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 497 (M+l)+. lR NMR δ (CD3OD): 0.68 - 1.17 (m, 8H), 1.58 -1.82 (m, 4H), 1.84 - 1.98 (m, 1H), 2.14 - 2.28 (m, 1H), 4.52 (bs, 1H), 6.38 (bs, 1H), 7.44 (ddd, 1H), 7.68 (dd, 1H), 8.15 (bs, 1H), 8.45 (s, 1H), 10.02 (bs, 1H). Example 116 (Phantom-2-(benzyloxy)-1-(3-(2-(6-fluoroimidazo[l,2-a])pyridin-3-yl)pyrimidin-4-ylamino) Piperidin-1-yl)ethanone

According to the experimental procedure as described in Example 95, from 2-(benzyloxy)acetic acid (28 μL, 0.19 mmol) and (i?)-2-(6-fluoroimidazo[1,2- a] 351 201130835 吼-3-yl) (唆-3-yl)^π定-4-amine (30 克, 0.1 mmol, Preparation 9b) gave a white solid (40 mg, 90%). LRMS (m/z): 461 (M+l)+. H NMR δ (CD3OD): 1.55 - 1.79 (m, 5H), 1.81 -1.95 (m, 1H), 2.09 - 2.22 (m, 3H), 2.89 (dd, 1H), 3.18 (t, 1H), 3.79 (d, 1H), 3.90 (d, 3H), 4.00 - 4.21 (m, 4H), 4.27 (d, 2H), 4.38 (bs, 2H), 4.51 - 4.59 (m, 1H), 4.60 (s, 2H ), 6.34 (d, 1H), 6.38 (d, 1H), 6.99 (bs, 3H), 7.08 (bs, 3H), 7.23 - 7.49 (m, 8H), 7.69 (ddd, 2H), 8.12 (d, 2H), 8.40 (s, 1H), 8.47 (s, 1H), 9.90 (bs, 1H), 10.02 (bs, 1H). Example 117 (Λ)-(3-(2-(6-fluoroimidazo[l,2-ap-pyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl) (7 ugly- Indole-2-yl)methanone

According to the experimental procedure as described in Example 95, from 1//-indole-2-carboxylic acid (31 mg, 0.19 mmol) and (phantom-2-(6-fluoroimidazo[1,2-a] Pyridin-3-yl)-AK piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 456 (M+l)+. ]H NMR δ (CD3OD): 1.79 (m, 4H), 2.04 (m, 2H), 352 201130835 2.12 - 2.26 (m, 2H), 3.55 - 3.74 (m, 1H), 3.93 - 4.20 (m, 1H) , 6.34 (b, 2H), 6.50 - 7.20 (m, 4H), 7.35 (t, 2H), 7.56 (bs, 2H), 8.04 (bs, 1H), 8.21 (bs, 1H), 9.72 (bs, 1H) ). Example 118 (Λ)-1-(3-(2-(6-fluoroimidazo[1,2-ap-pyridin-3-yl)pyrimidin-4-ylamino)) Bite _1_ base)-5 -(4-Phenylphenyl)戍-1-嗣

According to the experimental procedure as described in Example 95, 5-(4-fluorophenyl)pentanoic acid (38 mg, 0.19 mmol) and (Λ)-2-(6-fluoroimidazo[1,2- a] Pyridin-3-yl)-AK piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. : 491 (M+1). NMR δ (CD3OD): 1.33 (m, 1H), 1.45 (m, 1H), 1.59 - 1.84 (m, 4H), 1.88 (m, 1H), 2.16 (m, 1H), 2.29 (t, 2H), 2.46 (t, 1H), 2.64 (t, 1H), 2.80 (dd, 1H), 3.10 - 3.24 (m, 1H), 3.46 (dd, 1H), 3.84 (d, 2H), 6.43 (d, 1H) , 6.74 - 6.83 (m, 1H), 6.83 - 6.91 (m, 1H), 6.96 (t, 1H), 7.19 (dd, 1H), 7.37 - 7.50 (m, 1H), 7.68 (dt, 1H), 8.09 - 8.17 (m, 1H), 8.19 (d, 1H), 8.42 (s, 1H), 8.48 (s, 1H), 10.00 (bs, 1H). Example 119 353 201130835 (magic _2_(2_ gas phenyl)_1_((Λ)_3_(2-(6-fluoroimidazo[l,2-a] oxaridin-3-yl)) Base) bite-1-yl)-2-thiophene

According to the experimental procedure as described in Example 95, (π)-2-(2-chlorophenyl)-2-hydroxyacetic acid (38 mg, 0.19 mmol) and (7^-2-(6-fluoro) M. 0 satisfies and [l,2-a]a is a white solid (by chito-3-yl), biting 4-amine (30 oz, 0.1 mmol, preparation 9b). 19 mg, 40%) LRMS (m/z): 481 (M+l) + .H NMR δ (CD3OD): 0.81 - 0.95 (m, 2H), 1.57 (m, 4H), 1.65 - 1.78 ( m, 4H), 1.86 - 1.96 (m, 1H), 1.98 - 2.08 (m, 1H), 2.13 (m, 1H), 2.86 (dd, 1H), 3.00 (dd, 1H), 3.08 - 3.20 (m, 1H), 3.59 (d, 1H), 3.81 (d, 1H), 3.89 - 4.08 (m, 1H), 4.11 -4.24 (m, 1H), 4.69 - 4.79 (m, 1H), 5.62 - 5.72 (m, 1H), 5.81 (s, 1H), 6.20 - 6.30 (m, 1H), 6.31 - 6.42 (m, 1H), 7.05 - 7.14 (m, 2H), 7.19 (t, 1H), 7.23 - 7.31 (m, 1H), 7.38 (d, 2H), 7.42 -7.55 (m, 5H), 7.72 (ddd, 2H), 8.08 (d, 3H), 8.39 - 8.59 (m, 2H), 9.94 - 10.12 (m, 1H) Example 120 (i?)-l-(3-(2-(6- odorant and [l,2-a]a than indol-3-yl)-inden-4-ylamino) brigade bite-1 -yl)-2-(methylamino)acetamethylene 354 201130835

According to the experimental procedure as described in Example 95, 2-(methylamino)acetic acid (36 mg, 0.192 mmol) and (fanta-2-(6-fluoroimidazo[l,2-a] acridine) -3-yl)-piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 384 (M+l)+. !H NMR δ (CD3OD): 1.54 - 1.83 (m, 2H), 1.83 -1.97 (m, 1H), 2.03 - 2.22 (m, 1H), 2.23 - 2.30 (m, 1H), 2.42 (bs, 3H) , 2.90 (dd, 1H), 3.12 - 3.25 (m, 1H), 3.33 - 3.43 (m, 1H), 3.49 (bs, 2H), 3.73 (d, 1H), 3.82 (dd, 1H), 4.59 (d , 1H), 6.39 (dd, 1H), 7.44 (dd, 1H), 7.68 (td, 1H), 8.03 - 8.23 (m, 1H), 8.42 (s, 1H), 8.47 (s, 1H), 9.88 - 10.11 (m, 1H). Example 121 (i?)-l-(3-(2-(6-fluoroimidazo[l,2-a]"pyridin-3-yl)pyrimidin-4-ylamino)) )-2-(2-methoxyethoxy)acetamidine

355 201130835 According to the experimental procedure as described in Example 95, from 2-(2-decyloxyethoxy)acetic acid (22 μL, 0.19 mmol) and fluoroimidazo[l,2-a]Bit^- 3-Jinchen-3-yl) Mouth bite 4-amine (3 mg, 〇1 mmol) <RTI ID=0.0></RTI> </ RTI> <RTIgt; LRMS (m/z): 429 (M+l)+. NMR δ (CD3OD): 1.52 - 1.80 (m, 2H), 1.83 - 1.99 (m, 1H), 2.11 - 2.21 (m, 1H), 2.91 - 3.01 (m, 1H), 3.09 - 3-27 (m, 2H), 3.37 (s, 3H), 3.41 - 3.45 (m, 1H), 3.45 - 3.53 (m, 1H), 3.59 (dd, 1H), 3.65 - 3.71 (m, 1H), 3.79 (d, 1H) , 3-89 (d, 1H), 4.28 (s, 2H), 4.50 (d, 1H), 6.31 - 6.48 (m, 1H), 7.45 (dd, 1H), 7.70 (td, 1H), 8.09 - 8.23 (m, 1H), 8.45 (d, 1H), 9.91 - 10.12 (m, 1H) 〇ijfcl_122 β)-1-(3·(2-(6-fluoroimidazo[i,2_a]pyridine_3_yl) Pyrimidine _4_ylamino) brigade)-2_(2.methylthiazol-4-yl)ethanone

According to the experimental procedure as described in Example 95, 2-(2-mercaptothiazolyl)acetic acid (31 mg, 0. 丨9 mmol) and (magic--2-(6-fluoroimidazolyl) bite · 3-yl) #(0- pyridine-3-yl)pyrimidin (3 mg, 0.1 356 201130835 mmol, Preparation 9b) afforded a white solid (29 mg, 66%). LRMS (m/z) : 452 (M+l)+.]H NMR δ (CD3OD): 1.57 - 1.77 (m, 4H), 1.87 (dt, 1H), 2.10 - 2.22 (m, 1H), 2.68 (s, 3H), 3.00 (dd, 1H), 3.76 (s, 2H), 3.92 (d, 2H), 4.01 (d, 1H), 4.51 (d, 1H), 6.39 (d, 1H), 7.00 (bs, 1H), 7.14 ( s, 1H), 7.36 - 7.50 (m, 1H), 7.68 (td, 1H), 8.15 (d, 1H), 8.33 - 8.48 (m, 1H), 9.97 (d, 1H). Example 123 (π)· (3·(2-(6·fluoroimidazo[l,2_a]acridin-3-yl)pyrimidin-4-ylamino) ketone-1-yl)(tetrazole-4-yl)-嗣

According to the experimental procedure as described in Example 95, tetrahydro-27/-piperidin-4-decanoic acid (25 mg, 0.19 mmol) and 〇R)-2-(6-fluoroimidazo[1, 2-a] Pyridin-3-yl)-indole; piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 425 (M+l)+. NMR δ (CD3OD): 1.53 - 1.99 (m, 6H), 2.10 -2.26 (m, 2H), 2.77 (dd, 1H), 2.85 - 3.06 (m, 1H), 3.44 - 3.59 (m, 2H), 3.68 - 3.77 (m, 1H), 3.82 - 3.91 (m, 1H), 3.96 (t, 2H), 4.17 (bs, 1H), 4.67 (d, 1H), 6.43 (d, 1H), 7.46 (dt, 1H ), 357 201130835 7.71 (ddd, 1H), 8.19 (d, 1H), 8.42 (s, 1H), 8.47 (s, 1H), 9.91 -10.08 (m, 1H). Example 124 (i?)-l-(3-(2-(6- odor 嗤[l,2-a]n ratio bit-3-yl)) ate-4-ylamino)piperidin-1- 2-(2-methyl-/and-benzo[d]imidazol-1-yl)ethanone

According to the experimental procedure as described in Example 95, 2-(2-methyl-17/-benzo[4-imidazol-1-yl)acetic acid (37 mg, 0.19 mmol) and (7^-2- (6- 就 米 唾 并 [l,2-a]n than 唆-3-yl) (Brigade -3-yl) ring bite 4-amine (30 mg, 0.1 mmol, preparation 9b) obtained White solid (20 mg, 43%). LRMS (m/z): 485 (M+l) +.H NMR δ (CD3OD): 1.64 - 1.79 (m,1 Η), 2.02 (m, 1H), 2.14 - 2.31 (m, 1H), 2.41 (s, 1H), 2.52 (s, 3H), 2.94 (m, 1H), 3.54 - 3.72 (m, 1H), 3.87 - 4.07 (m, 1H), 4.56 (d , 1H), 5.14 - 5.36 (m, 2H), 6.35 (d, 1H), 6.54 (d, 1H), 7.08 - 7.16 (m, 1H), 7.21 (td, 1H), 7.31 - 7.51 (m, 1H ), 7.52 - 7.58 (m, 1H), 7.65 (td, 1H), 8.11 (d, 1H), 8.25 (d, 1H), 8.40 (s, 1H), 8.47 (s, 1H), 9.85 - 10.11 ( m, 1H). Example 125 10-Alk-3-yl ((Λ)-3-(2-(6-fluoroimidazo[l,2-a] acridine-3-yl)pyrimidine 358 201130835 -4-yl Amino) brigade bite-1-yl) formazan

According to the experimental procedure as described in Example 95, K) alkano-3-decanoic acid (34 mg, 0.19 mmol) and (i〇-2-(6-fluoroimidazo[l,2-a]pyrene) Pyridin-3-yl)-indole: piperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 473 (M+l)+. lK NMR δ (CD3OD): 1.58 - 2.02 (m, 4H), 2.08 -2.26 (m, 2H), 2.76 - 3.14 (m, 2H), 3.46 - 3.72 (m, 1H), 3.74 -4.10 (m, 4H ), 4.27 - 4.46 (m, 1H), 6.44 (dd, 1H), 6.54 - 6.64 (m, 1H), 6.68 - 6.80 (m, 1H), 6.80 - 6.89 (m, 1H), 6.98 - 7.16 (m , 1H), 7.37 - 7.50 (m, 1H), 7.67 (d, 1H), 8.16 (dd, 1H), 8.28 (bs, 1H), 8.49 (s, 1H), 9.98 - 10.08 (m, 1H). Example 126 (7?)-7V-(2-(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidine-1 -yl)-2-oxoethyl)-7V-methylbenzamide 359 201130835

According to the experimental procedure as described in Example 95, 2-(7V-methylbenzimidino)acetic acid (37 mg, 0.19 mmol) and (and)-2-(6-fluoroimidazo[1] , 2-a]n is a white solid (36 mg, 77%) as a white solid (3 mg, 77%). 488 (M+l)+. 'H NMR δ (CD3OD): 1.50 - 2.02 (m, 4H), 2.07 -2.26 (m, 1H), 2.97 (s, 2H), 3.04 (s, 3H), 3.12 ( s, 1H), 3.72 -4.04 (m, 1H), 4.09 - 4.42 (m, 2H), 6.33 - 6.44 (m, 1H), 6.45 -6.52 (m, 1H), 7.20 - 7.35 (m, 1H), 7.35 - 7.55 (m, 5H), 7.62 -7.77 (m, 1H), 8.07 - 8.23 (m, 1H), 8.47 (bs, 1H), 10.00 - 10.12 (m, 1H). Example 127 (Λ)-2 -(3-chlorophenoxy)-1-(3_(2-(6-fluoroimidazo[l,2-a] «bipyridin-3-yl)-n-butyl-4-ylamino)-bite- 1-base)

360 201130835 according to the experimental procedure as described in Example 95, from 2-(3-phenoxy)acetic acid (36 mg, 0.19 mmol) and (7^-2-(6-fluoroimidazo[1, 2-a] Pyridin-3-yl)-7V-(piperidin-3-yl)pyrimidin-4-amine (30 mg, 0.1 mmol, mp. (m/z): 481 (M+l)+ NMR δ (CD3OD): 1.56 - 1.85 (m, 4H), 1.87 -2.01 (m, 2H), 2.11 - 2.19 (m, 2H), 2.20 (s , 2H), 2.98 (t, 2H), 3.45 - 3.57 (m, 2H), 3.7 (m, 2H), 3.73 - 3.93 (m, 2H), 4.47 -4.67 (m, 2H), 6.37 (d, 1H ), 6.44 (d, 1H), 6.52 - 6.61 (m, 1H), 6.61 - 6.72 (m, 2H), 6.81 - 7.01 (m, 4H), 7.03 (t, 1H), 7.15 -7.32 (m, 1H) ), 7.35 - 7.50 (m, 2H), 7.63 (dd, 2H), 8.16 (d, 2H), 8.38 (s, 1H), 8.46 (s, 1H), 9.86 - 9.95 (m, 2H), 9.97 - 10.08 (m, 1H). Example 128 (1?)-1-(3-(2·(6-fluoroimidazo[l,2-a]°pyridin-3-yl)pyrimidin-4-ylamino )Brigade bite base)_2,2_double (via sulfhydryl)butyl-1-copper

According to the experimental procedure as described in Example 95, from 2,2-bis(hydroxyindenyl)butyric acid (29 mg, 0.19 mmol) and (Λ)-2-(6-fluoroimidazo[1,2 -a] Pyridin-3-yl)-7V-(piperidin-3-yl)pyrimidin-4-amine (30 mg, 0.1 mmol, s </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; LRMS (m/z): 443 (M+l)+. !H NMR δ (CD3OD): 0.89 (t, 3Η), 1.51 - 1.81 (m, 6H), 1.90 (dd, 1H), 2.07 - 2.23 (m, 1H), 3.69 - 3.92 (m, 7H), 3.97 - 4.10 (m, 1H), 4.20 - 4.38 (m, 2H), 6.38 (bs, 1H), 7.45 (ddd, 1H), 7.69 (dd, 1H), 8.15 (bs, 1H), 8.46 (s, 1H) ), 10.04 (bs, 1H). Example 129 (i?)_l-(3-(2-(6-fluoroimidazo[l,2-a]«bipyridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yltetrayl Oxazol-5-yl)ethanone

According to the experimental procedure as described in Example 95, from 2-(2//-tetrazol-5-yl)acetic acid (25 mg, 0.19 mmol) and (7^)-2-(6-fluoroimidazolium) [1,2-a]pyridin-3-yl)-AKpiperidin-3-yl)pyrimidine-4-amine (30 mg, 0.1 mmol, mp. LRMS (m/z): 423 (M+l)+. ]H NMR δ (CD3OD): 1.52 - 1.95 (m, 4H), 2.02 -2.22 (m, 1H), 3.33 (s, 2H), 3.72 - 3.87 (m, 1H), 3.87 - 4.29 (m, 4H) , 4.35 - 4.46 (m, 1H), 6.42 (bs, 1H), 7.43 (d, 1H), 7.67 (dd, 1H), 8.14 (bs, 1H), 8.43 (d, 1H), 10.01 (bs, 1H ). 362 201130835 Example 130 iV (1 (1 ugly - 1 '2, 4 · 3 嗓 · 3 _)) Bite -3- base) -2- (6-fluoro-bite [1,2-»] ° ratio Bite-3-yl) bite _4_amine,

(8)-2-(6-fluoroimidazo[l,2-a]pyridyl-3-yl)(piperidin-3-yl)pyrimidine-4-amine (42 mg, 〇13 mmol) at 150 °C Preparation of 9b) and 3-Demo]仏124_triazole (1〇mg, 〇〇7亳mol, prepared as described in J. Med. Chem. 2004, 47(19), 4645-4648) Overnight. Directly by reverse phase chromatography (from Waters C-18 dioxide dream, water / 1:1 acetonitrile - methanol as a dissolving agent [via 〇 1〇 / 〇 v / v formic acid buffer] 〇 0 / 〇 to 100 The title compound (4 mg, 15%) was obtained. LRMS (m/z): 380 (M+l)+. H-NMR δ (CDC13): 1.8 (m, 2H), 1.9 (m, 1H), 2.0 (ms 1H), 3.2 (m, 1H), 3.3 (m, ih), 3.7 (m, 1H), 4.1 (m, 2H), 5.2 (bs, 1H), 6.1 (m, 1H), 7.2 (m, 1H), 7.6 (dd, 1H), 7.8 (m, 1H), 8.1 (m, 1H), 8.5 (s, 1H), 9.8 (m, ih). Example 131 (10-2-(3-(2-(6-fluoroimidazo[12-fl]pyridine-3-yl)pyrimidin-4-ylamine 363 201130835))piperidin-1-yl)thiazole-5-carbonitrile

According to the experimental procedure as described in Example 130, 2-bromothiazole-5-indolecarbonitrile (50 mg '0.26 mmol) and (8)-2-(6-fluoroimidazo[l,2-a]pyridine- 3-Methyl)-A-piperidin-3-yl)pyrimidine-4-amine (125 mg, 0.4 mmol, mp. LRMS (m/z): 421 (M+l)+. H-NMR δ (CDC13): 1.8 (m, 2H), 2.0 (m, 2H), 2.1 (m, 1H), 3.3 (dd, 1H), 3.4 (m, 1H), 3.7 (m, 1H) , 4.3 (dd, 1H), 5.3 (d, 1H), 6.2 (d, 1H), 7.2 (m, 1H), 7.6 (m, 2H), 8.2 (d, 1H), 8.6 (s, 1H), 9.9 (dd, 1H). Example 132 (i?)-l-(〇R)-3_(2-(6-fluoroimidazo[l,2-a]&quot;bipyridin-3-yl)pyrimidin-4-ylamino) brigade bite -I-yl)-2,3-di-propyl-1-pyrene

364 201130835 According to the experimental procedure as described in Example 95, (and) 2,2-dimercapto-1,3-dioxolan-4-carboxylic acid (120 mg '0.82 mmol) and (and) -2-(6-fluoroρmβ sits and [1,2-3]° is more than -3- base)--(Nice -3-K) spray π定_4-amine (220 mg ' 0.67 毫Moer's Preparation 9b) gave a white solid (66 mg, 6 〇 / 〇), then treated with acetic acid. LRMS (m/z): 401 (M+l)+. Η NMR δ (DMSO-i/6): 1.41 - 1.69 (m, 4H), 1.72 - 1.86 (ώι, lH), 2.00 - 2.18 (m, 1H), 2.59 - 2.76 (m, 1H), 2.99 - 3.19 (m, 1H), 3.42 - 3.67 (m, 2H), 3.76 - 4.45 (m, 2H), 4.53 - 4.79 (m, 1H), 4.80 - 5.01 (m, 1H), 6.40 (bs, 1H), 7.52 (t, 2H), 7.80 (dd, 1H), 8.20 (bs, 1H), 8.36 - 8.66 (m, 1H), 9.96 (bs, 1H) ° ? Example 133 (5)-1-((and) -3-(2-(6-fluoroimizolo[i,2-a]-flavor-3-yl) mouth bite·4·ylamino)piperidin-1-yl)-2,3-dihydroxy Propane-ketone

According to the experimental procedure as described in Example 132, from dimethyl:1,3-dioxolan-4-carboxylic acid (59 mg, 0.39 mmol) and (magic _2_(1 fluoroimidazo[1, 2_a]n-pyridyl)Nan(Bisidine·3_yl)pyrimidine|amine ((10) gram, 0.32 mmol, %) obtained as a white solid (68 mg, 365 201130835 53%) ° LRMS (m/z ): 401 (M+l)+. !H NMR δ (DMSO-4): 1.58 (m, 2H), 1.70 - 1.84 (m, 1H), 2.01 - 2.16 (m, 1H), 2.58 - 2.78 (m , 1H), 2.90 - 3.21 (m, 1H), 3.37 - 3.66 (m, 2H), 3.76 - 4.19 (m, 2H), 4.26 - 4.50 (m, 1H), 4.55 - 4.79 (m, 2H), 4.88 (bs, 1H), 6.40 (d, 1H), 7.52 (dd, 2H), 7.80 (dd, 1H), 8.10 - 8.30 (m, 1H), 8.37 - 8.62 (m, 1H), 9.97 (bs, 1H) Example 134 (Λ)-3-(3-(2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-5-methylpyrimidin-4-ylamino)) ratio Lozen-1-yl)-3 side oxycaline

According to the experimental procedure as described in Example 46, (7^)-2-(6-fluoroimidazo[1,2-&amp;]0 is more than -3-yl)-5-fluorenylpyridine 0 3-ylamine (78 mg, 0.25 mmol, preparation 48b) and 3-[(2,5-di-oxypyrrolidin-1-yl)oxy]-3-oxo-propanenitrile (68) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ]H NMR δ (CDC13): 1.11 - 1.49 (m, 2H), 2.12 (s, 366 201130835 3H), 2.35 (m, 2H), 3.43 - 3.78 (m, 3H), 3.81 - 4.06 (m, 1H) , 4.72 - 5.05 (m, 1H), 5.58 - 6.03 (m, 1H), 7.24 (bs, 1H), 7.67 (bs, 1H), 8.08 (d, 1H), 8.47 (s, 1H), 9.99 (bs , 1H). Example 135 ($)-2-(6-odor salino[l,2-a]n is more than -3-yl) gas D is more than bite-2_yl)ethyl)-5-methylpyrimidin-4-amine

According to the experimental procedure as described in Preparation 5a, from 2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-5-mercaptopyrimidine-4-ol (75 mg, 0.31 m Preparation of 19b) and 〇S)-l-(5-fluoropyridin-2-yl)ethylamine hydrochloride (108 mg, 0.61 mmol, as described in WO2006/82392) afforded a white solid ( 20 mg, 18%). LRMS (m/z): 367 (M+l)+. lR NMR δ (CDC13): 1.66 (d, 3H), 2.17 (s, 3H), 5.50 (t, 1H), 5.94 (d, 1H), 7.20 (ddd, 1H), 7.38 - 7.44 (m, 2H) , 7.65 (dd, 1H), 8.08 (s, 1H), 8.45 (s, 1H), 8.48 (s, 1H), 9.90 (dd, 1H) 〇 Example 136 2-(6-fluoroimidazo[1,2 -a] acridine-3-yl)-Λ^-((5-fluoroacridin-2-yl)methyl)pyrimidine-4,5-diamine 367 201130835

Will / carbon (10%, 48 mg, 0 ^ $ Fluorine rice _i, 2 · Shiling 3_ base $ = (6-based _4_amine (113 mg, 〇 29 mmol) Base -5 - hydrazine (15 ml) in suspension and at ambient temperature in gas = bis = 2 hours. Filter the mixture via Celite® and wash the filter cake with ethanol. Evaporate the combined filtrate and knee wash to produce The title compound (88 mg, 96%), m.j. , 2H), 7.41 (dd, 1H), 7.47 - 7.61 (m, 2H), 7.71 (td, 2H), 7.79 (s, 1H), 8.15 (s, 1H), 8.56 (d, 1H), 9.65 ( Dd, 1H). Example 137 2-(6-fluoroimidazo[l,2-a]e-pyridyl-3-yl)-A^-(5,6,7,8-tetrahydroquinolin-5· Pyrimidine-4,5-diamine

368 201130835 According to the experimental procedure as described in Example 136, by #-(2-(6-fluoromethane 0 sits and [l,2-a]n is more than -3-yl)-5-nitro-snack- 4-Base)-5,6,7,8-tetrahydroindol-5-amine (Preparation 50) gave a pale green solid (94%). LRMS (m/z): 376 (M+l)+. NMR (300 MHz, DMSO-i/6) δ ppm 1.90-2.16 (m, 4H), 2.93 (m, 2H), 5.08 (br s, 2H), 5.58 (dd, 1H), 6.99 (d, 1H) , 7.20 (dd, 1H), 7.42 (ddd, 1H), 7.67 (d, 1H), 7.74 (dd, 1H), 7.76 (s, 1H), 8.22 (s, 1H), 8.41 (dd, 1H), 9.91 (dd, 1H). Example 138 (i?)-2_(6-fluoroimidazo[1,2-a]acridin-3-yl)methylbutan-2-ylpyrimidine-4,5-diamine

According to the experimental procedure as described in Example 136, (i?)-2-(6-fluoromistine sits and [1,2-a]π is sigma-3-yl)-7V~(3-A Ketidin-2-yl)-5-nitropterin-4-amine (Preparation 51) gave a pale brown solid (114 mg, 99%). LRMS (m/z): 315 (M+l)+. HNMR δ (DMS0-4): 〇·94 (dd, 3H), 1.01 (t, 3H), 1.20 (dd, 3H), 1.91 - 2.11 (m, 1H), 4.12 - 4.28 (m, 1H), 5.02 -5.16 (m, 2H), 6.35 (d, 1H), 7.35 - 7.50 (m, 1H), 7.65 - 7.71 369 201130835 (m,1H), 7.75 (dd,1H), 8.16 - 8.25 (m, 1H ), 9.95 (dt, 1H). Example 139 2-(6-Fluoroimidazo[l,2-a]pyridin-3-yl)methoxypropan-2-yl)pyrimidine-4,5-diamine

According to the experimental procedure as described in Example 136, 2-(6-fluoroimidazo[1,2-appyridin-3-yl)-AK1-methoxypropan-2-yl)-5-nitro Pyrimidine-4-amine (115 mg, 0.33 mmol, mp. LRMS (m/z): 317 (M+l)+. lU NMR δ (OMSO-d6): 1.28 (d, 3H), 3.32 (s, 3H), 3.38 -3.42 (m, 1H), 3.49 - 3.62 (m, 1H), 4.26 - 4.57 (m, 1H), 5.07 (s, 2H), 6.45 (d, 1H), 7.42 (dd, 1H), 7.74 (dd, 2H), 8.19 (s, 1H), 9.91 (dd, 1H). Example 140 2-((lr,4/〇-4-(5-Amino-2-(6-fluoroimidazo[1,2-a]&quot;bipyridin-3-yl)pyrimidin-4-ylamino) Cyclohexyl)acetonitrile 370 201130835

According to the experimental procedure as described in Example 136, from 2-(( 1 r,4r)-4-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-5- Nitropyrimidin-4-ylamino)cyclohexyl)acetonitrile (Preparation 53) gave a pale green solid (92%). LRMS (m/z): 366 (M+l)+. !H NMR δ (CDC13): 1.26 - 1.47 (m, 4H), 1.79 (m, 1H), 2.05 (m, 2H), 2.36 (d, 4H), 3.06 (br s, 2H), 4.06 (m, 1H), 4.85 (d, 1H), 7.21 (ddd, 1H), 7.66 (dd, 1H), 7.89 (s, 1H), 8.43 (s, 1H), 9.95 (dd, 1H). Example 141 (l/*, 4r)-4-(5-Amino-2-(6-fluoroimidazo[l,2-fl]pyridin-3-yl)pyrimidin-4-ylamino)-1- Methylcyclohexanol

According to the experimental procedure as described in Example 136, from (lr, 4r)-4-(2-(6-gas pm-disindol [1,2-a]π-biti-3-yl)-5-stone base Mouthion-4-ylamino)-1-decylcyclohexanol (110 mg, 0.23 mmol, Preparation 54) afforded a white solid solid 371 201130835 (51%). LRMS (m/z): 357 (M+l)+. H-NMR δ (DMSO-i/6): 1.2 (s, 3H), 1.4-1.7 (m, 6H), 2.0 (m, 2H), 4.0 (bs, 1H), 4.4 (s, 1H), 5.0 (s, 2H), 6.4 (d, 1H), 7.4 (m, 1H), 7.7 (s, 1H), 7.7 (dd, 1H), 8.2 (s, 1H), 9.9 (dd, 1H). Example 142 2-(6-fluoroimidazo[1,2-a]&quot;bipyridin-3-yl)-7V^-(1_(5-fluoroacridin-2-yl)-2-methoxyethyl) Pyrimidine-4,5-diamine

According to the experimental procedure as described in Example 136, 2-(6-fluoroimidazo[1,2-a]α is more than _3_base gas π-bit-2-yl)-2-oxiranyloxy -5-Shishasylpyrimidin-4-amine (142 mg, 0.33 mmol, Preparation 55) afforded a pale brown solid (87%), followed by flash chromatography (1-5% dec. The crude product was purified. LRMS (m/z): 398 (M+l)+. H NMR δ (DMSO-i/6): 3.35 (s, 3H), 3.75 - 3.93 (m, 1H), 5.28 (s, 2H), 5.46 - 5.63 (m, 1H), 7.14 (d, 1H ), 7.42 (dd, 1H), 7.55 - 7.63 (m, 1H), 7.66 - 7.81 (m, 4H), 8.02 - 8.18 (m, 1H), 8.53 - 8.64 (m, 1H), 9.56 - 9.74 (m , 1H). 372 201130835 Example 143 (5)-2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-4-(1-(5-fluoropyridin-2-yl)ethylamino)pyrimidine -5-formic acid

A solution of lithium hydroxide monohydrate (61 mg, 1.45 mmol) in water (2 mL) was added to 〇S&gt;2-(6-fluoroimidazo[l,2-a]acridin-3-yl)- 4-(1-(5-gas π ratio π-but-2-yl)ethylamine) mouth bite-5-capric acid B from the purpose (62 house grams, 0.15 millimoles, preparation 57) in decyl alcohol (10 The resulting mixture was stirred for 1 hour at room temperature in a solution of ML) and THF (8 mL). The solvent was evaporated under reduced pressure and the residue was diluted with water. After addition of 2 Ν aqueous hydrochloric acid solution to pH = 4, a solid precipitated, which was filtered and dried in vacuo to give 54 mg (93%). LRMS (m/z): 397 (M+l)+. lR NMR δ (DMSO-i/6): 1.61 (d, 3H), 3.13 - 3.53 (m, 1H), 5.36 - 5.70 (m, 1H), 7.36 - 7.98 (m, 4H), 8.38 - 8.66 (m , 1H), 8.86 (bs, 1H), 9.14 (bs, 1H), 9.70 (bs, 1H), 13.23 - 13.66 (m, 1H). Example 144 (5)-2-(6-fluoroimidazo[1,2-&lt;ι]°pyridin-3-yl)-4-(1-(5-fluoroacrididine-2-373 201130835) Ethyl)pyrimidine-5-carboxamide

Add ΛΚ3-dimethylaminopropyl)W-ethylcarbodiimide hydrochloride (138 mg, 0.72 mmol) and 1-hydroxybenzotriazole (97 mg, 0.72 mmol) to hydrazine S&gt;2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-4-(1-(5-fluoroacridin-2-yl)ethylamino)pyrimidine-5-carboxylic acid (190 mg, 0.48 mmol, Example 143) in dimethylformamide (7 mL) and the mixture was stirred at room temperature for half an hour. An aqueous solution of ammonium hydroxide (28 μL, 0.71 mmol) was then added and the reaction mixture was stirred at room temperature overnight. Water was added and a solid precipitated which was filtered and washed with water. After drying under vacuum at 50 ° C, 140 mg (74%) of title compound. LRMS (m/z): 396 (M+l)+. !H-NMR δ (DMSO-^): 1.6 (d, 3H), 5.5 (m, 1H), 7.5 (m, 2H), 7.6 (m, 1H), 7.8 (dd, 1H), 8.4 (s, 1H), 8.5 (d, 1H), 8.8 (s, 1H), 9.7 (bs, 2H). Example 145 (5)-2-(6-Fluoroimidazo[l,2w]pyridin-3-yl)-4-((1-(5-fluoropyridin-2-yl)ethyl)(indenyl)amine Pyrimidine-5-formic acid 374 201130835

Sodium hydride (60% hexane suspension, 38 mg, 0.95 mmol) was added to (5&gt;2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-4-( Ethyl 1-(5-fluoroacridin-2-yl)ethylamino)pyrimidine-5-decanoate (200 mg, 0.47 mmol, Preparation 57) ΑΓ-dimercaptoamine (4 ml) The resulting mixture was stirred for 15 minutes at room temperature. Then iodonane (44 μl, 0.71 mmol) was added and the mixture was heated overnight at 60 ° C. After cooling to room temperature, the reaction mixture was poured over Stir on water for half an hour. Filter the precipitated solid, dry and by reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 acetonitrile-nonanol as eliminating agent [via 0.1% v/ Purification with v-acid buffer [0% to 100%) gave the title compound (11 mg, 5%). LRMS (m/z): 411 (M+l) +. ^-NMR δ (CDC13): 1.8 (m) , 3H), 2.9 (s, 3H), 6.2 (q, 1H), 7.3 (m, 1H), 7.4 (m, 2H), 7.8 (dd, 1H), 8.4 (s, 1H), 8.5 (s, 1H), 8.9 (s, 1H), 9.8 (dd, 1H). Example 146 2-(6-fluoroimidazo[1,2-&lt;ι] aridin-3-yl)-4-decapyridin-3 -methylamino)pyrimidine-5-decanoic acid 375 201130835

According to the experimental procedure as described in Example 143, from 2-(6-fluoroimiphth[1,2-a]pyridin-3-yl)-4-(pyridin-3-ylindenyl)pyrimidine-5 Ethyl citrate (520 mg, 1.33 mmol, Preparation 58) gave a solid (57%). LRMS (m/z): 365 (M+l)+. 'H-NMR δ (DMSO-^): 4.8 (d, 2H), 7.3 (dd, 1H), 7.5 (t, 1H), 7.8 (m, 2H), 8.4 (d, 1H), 8.5 (s, 1H), 8.6 (s, 1H), 8.8 (s, 1H), 9.0 (s, 1H), 9.6 (d, 1H). Example 147 2-(6-Fluoroimidazo[l,2-tf]acridin-3-yl)-4-(pyridin-3-ylmethylamino)pyrimidine-5-carboxamide

According to the experimental procedure as described in Example 144, from 2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-4-(pyridin-3-ylmethylamino)pyrimidine _5_ Formic acid (230 mg '0.63 mmol, Example 146) gave a solid (24%). 376 201130835 LRMS (m/z): 364 (M+l)+. H-NMR δ (DMSO-^6): 4.8 (d, 2H), 7.3 (dd, 1H), 7.5 (m, 1H), 7.6 (bs, 1H), 7.8 (m, 2H), 8.2 (bs , 1H), 8.4 (dd, 1H), 8.5 (s, 1H), 8.6 (d, 1H), 8.8 (s, 1H), 9.6 (t, 1H), 9.7 (dd, 1H)° Example 148 2- (6-fluoroimidazo[l,2-ii]pyridin-3-yl)-4-((5-fluoropyridin-2-yl)methylamino)pyrimidine-5-decanoic acid

According to the experimental procedure as described in Example 143, from 2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-4-((5-fluoroacridin-2-yl)indole Ethyl)pyrimidine-5-carboxylic acid ethyl ester (280 mg, 0.68 mmol, Preparation 59) gave a solid (25%). LRMS (m/z): 383 (M+l)+. !H-NMR δ (DMSO-J6): 4.9 (d, 2H), 7.5 (m, 2H), 7.7 (m, 1H), 7.8 (dd, 1H), 8.5 (s, 1H), 8.5 (d, 1H), 8.8 (s, 1H), 9.4 (s, 1H), 9.6 (dd, 1H), 13.4 (bs, 1H). Example 149 2-(6-Fluoroimidazo[1,2-indole]pyridin-3-yl)-4-((5-fluoropyridin-2-yl)methylamino)pyrimidine-5-decylamine 377 201130835

According to the experimental procedure as described in Example 144, from 2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)-4-((5-fluoropyridin-2-yl)indolyl Pyrimidine-5-carboxylic acid (38 mg, 0.10 mmol, Example 148) gave a solid (37%). LRMS (m/z): 382 (M+l)+. ^-NMR δ (DMSO-J6): 4.9 (d, 2H), 7.5 (dd, 1H), 7.7 (m, 2H), 7.9 (dd, 1H), 8.3 (d, 1H), 8.5 (d, 1H) ), 8.6 (s, 1H), 8.8 (s, 1H). Example 150 (S)-2-(6-Fluoroimidazo[l,2-a]acridin-3-yl)-4-(1-(4-fluorophenyl)butylaminopyrimidine-5-carboxylic acid

According to the experimental procedure as described in Example 143, 〇S&gt;2-(6-fluoromistine sits and [1,2-a]π is more than -3-yl)-4-( 1-(4-gas Phenyl) butylamino) mouth bite-5 - ethyl decanoate (470 mg, 0.71 mmol, preparation 60) gave a solid (52%). 378 201130835 LRMS (m/z): 424 (M+l)+. H NMR δ (DMSO-4): 〇-93 (t, 3H), 1.21 - 1.51 (m, 2H), 1.77 - 2.06 (m, 2H), 5.19 - 5.38 (m, 1H), 7.16 (t, 2H), 7.50 (dd, 1H), 7.59 (dd, 1H), 7.84 (dd, 1H), 8.49 (s, 1H), 8.84 (s, 1H), 9.02 (bs, 1H), 9.68 (d, 1H) ), 13.51 (bs, 1H). Example 151 (5)-2-(6-Fluoroimidazo[1,2-ίφ-pyridin-3-yl)-4-(1-(4-fluorophenyl)butylamino)pyrimidine-5-carboxamidine amine

According to the experimental procedure as described in Example 144, (S)-2-(6-fluoromethane and [1,2-&amp;]° ratio -3-yl)-4-(1-(4) - Gas phenyl) butylamine) Nitrate-5-carboxylic acid (160 mg, 0.38 mmol, Example 150) afforded a solid (37%). LRMS (m/z): 423 (M+l)+. ^-NMR δ (CDC13): 1.0 (t, 3H), 1.3-1.5 (m, 2H), 1.8-2.0 (m, 2H), 5.2 (m, 1H), 5.7 (bs, 2H), 7.0 (m , 2H), 7.2 (m, 1H), 7.4 (m, 2H), 7.7 (dd, 1H), 8.5 (s, 1H), 8.5 (s, 1H), 9.4 (d, 1H), 9.7 (dd, 1H). Example 152 4-((lr,4r)-4-(cyanoindolyl)cyclohexylamino)-2-(6-fluoroimidazolyl 379 201130835 [1,2-α]pyridin-3-yl)pyrimidine- 5-carboxylic acid

According to the experimental procedure as described in Example 143, 4-((lr,4r)_4_(cyanoindolyl)cyclohexylamino)-2-(6-fluoro.carbazino[ι,2-φ-pyridinium] _3_yl)pyrimidine·5_ethyl decanoate (90 mg '0.19 mmol) was obtained as a solid (72%). LRMS (m/z): 395 (M+l)+. H-NMR δ (DMSO-^): 1.1-1.5 (m, 4H), 1.7 (m, 1H), 1.9 (d, 2H), 2.2 (d, 2H), 2.5 (d, 2H), 4.0 ( m, 1H), 7.6 (m, 1H), 7.9 (m, 1H), 8.4 (d, 1H), 8.5 (s, 1H), 8.8 (s, 1H), 9.9 (m, 1H), 13.4 (s , 1H). Example 153 4-((lr,4r)-4-(cyanomethyl)cyclohexylamino)-2-(6-fluoroimidazo[l,2-ii]pyridin-3-yl)pyrimidine-5- Formamide

380 201130835 according to the experimental procedure as described in Example 144 'from 4-((lr,4r)-4_(cyanomethyl)cyclohexylamino)-2-(6-fluoroimidazo[1,2-a ]a-pyridin-3-yl)-pyridin-5-decanoic acid (34 mg, 0.09 mmol, Example 152) gave a solid (59%). LRMS (m/z): 394 (M+l)+. ^-NMR δ (CDC13): 1.4 (m, 4H), 1.8 (s, 1H), 2.0 (d, 2H), 2.3 (d, 4H), 4.1 (m, 1H), 5.6 (m, 2H), 7.3 (m, 1H), 7.7 (m, 1H), 8.5 (s, 1H), 8.6 (s, 1H), 8.7 (m, 1H), 9.9 (s, 1H). Example 154 (¢^)-2,2-dimethyl-1,3-dioxoindol-4-yl) ((and)-3-(2-(6-gascarbazolo[1,2·吡啶]]pyridin-3-yl)-5-methylpyrimidin-4-ylamino)piperidin-1-yl)methanone

According to the experimental procedure as described in Example 95, (2), 2, dimethyl, 1,3, dioxolane _4. decanoic acid (120 mg, 0.82 Torr) and (8)-2- (6- defeat ° meters ° sit and [1,2-&lt;3] ° bite · 3-base) _5_ 曱基善ς bite winter base) cancer bite 4-amine (22 〇 mg, 〇· Preparation of 20b), obtained as a white solid (160 mg, 52%), followed by reverse phase chromatography (c_i8 cerium oxide from Waters, water A: 1 acetonitrile decyl alcohol as eliminator) 〇 1% v/v formic acid slow 381 201130835 rush] 0% to 100%) purified. LRMS (m/z): 455 (M+l)+. 'H-NMR δ (CDC13): 1.1-1.4 ΤΤΛ ; 6m i 7 rm, 2H), 2.0 (m, 5H), 3.0 (m, 1H), 3.5-5 (m, 8H) 7 /), 丨 ( Two im examples 155 Wl.-3-(2-(6-fluorine and u-pyrimidine _4_ylamino) brigade -1 · base) -2,3_ two Xiang Fu Jlfc bite 3 correct 1 C - 1-ketone

In the armpits, the age of 2,2•diyl·3-(2 is similar to 坤 似 似 ' ' 心 心 心 心 氧 氧 氧 ( ( ( ( ( ( ( 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 ML) with water (2.5 mA = heating at 1.5 *. New solvent and by reverse phase layer (four) secret C-18 cerium oxide, water / 1:1 acetonitrile-methanol as ^ from Waters formic acid buffer] 0% The crude product was purified to give the title compound (65 mg, 60%). Color solid state LRMS (m/z): 415 (M+l)+. 'H-NMR δ (CDC13): 1.6-1.9 (m, 2H), 2. 〇 (m, 2H), 3.7-4.1 (m, 6H), 4.4 (m, 2H), 5.0 (m (m, sentence) ), 3 6 1 lean), 7) (t, 382 201130835 1H), 7.7 (dd, 1H), 8.0 (s, 1Η), 8.5 (m, 1H), 9.9 (d, 1H). Example 156 (Fantasy_3_(3_(5-Amino-2-(6-fluoroimidazo[1,2_&lt;ϊ] acridine-3-yl)pyrimidin-4-ylamino)) )_3·lateral oxygen cyan

〇R)-3-(3-(2-(6-fluoroimidazo[1,2-β]acridin-3-yl)-5-) Base) ketone-1-yl)-3-oxo-propion (60 oz, 0.14 mmol, preparation 62c) and tin dichloride dihydrate (130 mg, 0.58 mmol) in ethanol (3 The solution in ml) was heated for 2 hours. After cooling, the reaction mixture was diluted with EtOAc EtOAc. The crude product was purified by EtOAc EtOAc EtOAc: LRMS (m/z): 395 (M+l)+. !H NMR δ (CDC13): 1.85 - 1.97 (m, 4H), 2.06 - 2.22 (m, 2H), 3.62 - 3.78 (m, 2H), 3.83 (m, 1H), 4.27 (d, 1H), 4.38 (d, 1H), 5.13 - 5.40 (m, 2H), 7.21 (dt, 1H), 7.66 (td, 1H), 7.91 (s, 1H), 8.35 (s, 1H), 8.46 (s, 1H), 9.88 (dd, 1H). Example 157 (_/?)-3·(3-(5-cyclopropyl-2-(6- odorant and [1,2·&lt;ι]0 to bite-3-yl) mouth 383 201130835 bite- 4-aminoamino) ketone-1-yl)-3-oxo-propion

According to the experimental procedure as described in Example 46, (i〇-5-cyclopropyl-2-(6-fluoro-flavored 0-[1,2-&lt;3]bit-3-yl)- (Breakfast-3-yl) mouth bite 4-amine (95 mg, 0.27 mmol, preparation 64b) and 3-[(2,5-di- oxo-pyrrolidin-1-yl)oxy - 3-oxopropanenitrile (59 mg, 0.32 mmol, prepared as described in BE 875 054 (A1)) afforded a white solid (69%) by flash chromatography (2 m. Purification of chlorodecane/methanol. LRMS (m/z): 420 (M+l) + .H NMR δ (CDC13): 0.61 (dd, 2 Η), 0.94 - 1.07 (m, 2H), 1.53 (td , 1H), 1.72 - 2.06 (m, 3H), 2.07 - 2.18 (m, 2H), 3.70 (t, 1H), 3.81 (dd, 1H), 3.98 (dd, 1H), 4.36 (ddd, 1H), 5.21 - 5.57 (m, 2H), 7.13 - 7.28 (m, 2H), 7.67 (td, 1H), 8.13 (s, 1H), 8.48 (s, 1H), 9.95 (ddd, 1H). Example 158 (7 ^)-4-(1-(2-Acetyradyl) brigade bite-3_ylamino)-2-(6-odor sprayed [l,2-d]a than bit-3-yl) Mouth bite-5-A guess 384 201130835

According to the experimental procedure as described in Example 46, from (7?)-2-(6-fluoroimidazo[l,2-fl]nt(j^-3-yl)-4-(旅〇定-3 -Amino group) 〇定-5-曱 guess (30 oz, 0.09 mmol, preparation 66b) and 3-[(2,5-di-oxypyrrolidin-1-yl)oxy]- 3-Phenyloxypropionitrile (20 mg, 0.11 mmol, prepared as described in BE 875 054 (A1)) afforded as a white solid (22%). Purification to ethyl acetate. LRMS (m/z): 405 (M+l) + l NMR δ (CDC13): 1.79 - 2.01 (m, 2H), 2.25 (d, 2H), 3.04 (dd, 1H ), 3.14 - 3.46 (m, 1H), 3.59 (s, 2H), 3.65 -3.97 (m, 1H), 4.20 - 4.47 (m, 1H), 4.66 (dd, 1H), 5.61 - 5.88 (m, 1H) ), 7.32 (td, 1H), 7.72 (dd, 1H), 8.53 (s, 1H), 8.57 (d, 1H), 8.71 (s, 1H), 9.75 (dd, 1H). Example 159 (and)- 3-(3-(2-(6-1) Junjun[l,2-d]0 is more than -3-yl)-5-(A-branched) cancer bite-4-ylamino) brigade bite -1-yl)-3-lateral oxypropyl 385 201130835

According to the experimental procedure as described in Example 46, (/^)-2-(6-fluoroimidazo[1,2-β]α is more than -3-yl)-5-(anthracenyl) Ππ定-3-yl) Mouth sigma-4-amine (30 mg, 0.08 mmol, preparation 68b) and 3-[(2,5-di- oxetidin-1-yl)oxy A 3-sided oxypropionitrile (17 mg, 0.09 mmol, prepared as described in BE 875 054 (A1)) gave a white solid (34%). LRMS (m/z): 458 (M+l)+. !H NMR δ (CDC13): 0.77 - 2.20 (m, 5H), 3.15 (s, 3H), 3.45 - 3.67 (m, 4H), 3.75 - 4.02 (m, 2H), 4.49 (bs, 1H), 7.30 - 7.43 (m, 1H), 7.75 (d, 1H), 8.53 - 8.86 (m, 2H), 9.76 -9.98 (m, 1H). Example 160 (Λ)-4-(1_(2-Cyanoethyl)piperidin-3-ylamino)-2_(6-fluoroimidazo[1,2-β]0-biti-3-yl ) °3⁄4 bite-5-formic acid ethyl vinegar

386 201130835 according to the experimental procedure as described in Example 46, from 〇R)-2-(6-fluoroimidazo[1,2-α] ° ratio α-3-yl)-4-(α bottom bite - 3-aminoamino) cancer bite-5· decanoic acid (80 mg, 0.21 mmol, preparation 69b) and 3-[(2,5-di- oxetidin-1-yl)oxy 3-Bottom-oxypropionitrile (46 mg, 0.25 mmol, prepared as described in BE 875 054 (A1)) afforded a white solid (96%). LRMS (m/z): 452 (M+l)+. NMR δ (CDC13): 1.42 (t,3Η), 1.74 - 2.30 (m, 4H), 3.26 (dd, 1H), 3.41 (s, 2H), 3.53 - 3.83 (m, 4H), 4.38 (q, 2H) ), 7.28 - 7.36 (m, 1H), 7.72 (td, 1H), 8.34 - 8.54 (m, 1H), 8.63 (s, 1H), 8.96 (s, 1H), 9.88 (dd, 1H). Example 161 (/?)-4-(l-(2-carbylethylidene) brigade-3-ylamino)-2-(6- odor and [1,2-&lt;1] 0 ratio Bite-3-yl) bite-5-formic acid

Add a solution of lithium hydroxide (47 mg, 1.12 mmol) in water (2 ml) to (and)-4-(1-(2-)-) Ethyl 2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)pyrimidine-5-decanoate (50 mg, 0.11 mmol, Example 160) in methanol (10 mL) 7 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 15 mg (32%) of the title compound LRMS (m/z): 424 (M+l) + NMR 5 (DMS0^6): 1.77 (bs, 3H), 2&gt;1〇(bs&gt; lH), 3.09 ( Dd,1H), 3.21 (d,1H), 3.55 (bs,1H),3 68 3 89 (m, 1H), 4.10 (s,2H), 4.39 (d,1H), 7.63 _,1H) 7 89 (Paper 1H), 8.41 8.60 (m, 1H), 8.66 (s, 1H), 8.87 9 9〇 (ddd, 1H), 13.47 (s, 1H). ' ^ Paste 162 (i?)_4-(l-(2-Cyanoethyl)piperidin-3-ylamino)·2(6-fluoroimidazo[1,2-α]pyridine-3- Pyrimidine-5-carboxamide

1-Pyryl pyrrolidine-2,5-dione (25 g, 〇22 mmol) and methylenedi-2-propan-2-amine (33 μl, 〇21 mM) at 0 °C Mole) is added to (8)-4-(1-(2-cyanoethenyl)pyrazine, 3, mei' 'imidazo[1,2-α]pyridin-3-yl)pyrimidine decanoic acid (1〇) 〇^克^ 2〇mmol, Example 161) Condition #- Dimercaptoamine (1 liter) solution. ' 201130835 Good mixture at room temperature overnight. Water (7 ml) was then added and the mixture was filtered and dried. The solid was redissolved in dioxane (1 ml) and aqueous ammonium hydroxide (30 μL) was added. After mixing for 5 hours at room temperature, water was added and the resulting solution was acidified by adding 2N aqueous hydrochloric acid. The resulting suspension was taken with a second gas mixture and the organic layer was separated, washed with 4% aqueous sodium carbonate and brine, dried over sodium sulfate and evaporated. Purification by reverse phase chromatography (from Waters c_18 ceria, water / 1:1 acetonitrile-methanol as the eliminator [pass 〇 1〇 / 〇v / v formic acid buffer] 0 〇 / 〇 to 100%) The crude product gave 3 mg (5%) LRMS (m/z): 423 (M+l)+. !H NMR δ (DMS〇-^6): 1.70 (ms&gt; 8H), 2.09 (m, 4H), 2.99 (dd, 1H), 3.20 (m&gt; 4H), 3.60 (m, 1H), 3.73 (m , 1H), 3.81 (m, 1H), 3.86 - 4.02 (m, 1H), 4.04 (d, 1H), 4.10 (d, 1H), 4.31 (m, 1H), 4.43 (dd, 1H), 7.60 ( Dd, 2H), 7.78 - 7.93 (m, 2H), 8.19 (bs, 2H), 8.62 (d, 2H), 8.85 (d, 2H), 9.24 (d, 1H), 9.33 (d, lH), 9.81 -9.92 (m, 1H). f Example 163 (and) -3-(3-(2-(6-----imidazo-p-pyridinyloxy)-yl)-yl) Propiononitrile 389 201130835

According to the experimental procedure as described in Example 46, (7?)-2-(6-fluoroimidazo[1,2-ίζ]π ratio -3-yl)-5-methoxy-7V-(旅0定-3-基) 咬--4-amine (210 mg, 0.61 mmol, preparation 71b) and 3-[(2,5-di-oxypyrrolidin-1-yl)oxy]- 3-Sideoxypropionitrile (134 mg, 0.74 mmol, prepared as described in BE 875 054 (A1)) gave a white solid (80%). LRMS (m/z): 410 (M+l)+. lH NMR δ (CDC13): 1.87 (d, 2H), 2.15 (m, 1H), 3.38 (d, 2H), 3.60 (m, 2H), 3.95 (s, 3H), 4.14 - 4.42 (m, 2H) , 5.21 -5.43 (m, 2H), 7.14 - 7.23 (m, 1H), 7.57 - 7.75 (m, 1H), 7.79 -7.93 (m, 1H), 8.36 (s, 1H), 8.47 (s, 1H) , 9.69 - 10.09 (m, 1H). Example 164 (^)-3-(3-(2-(6-fluoroimidazo[1,2-ii]pyridin-3-yl)-6-(7 ugly-1,2,4-triazole-1 -yl)pyrimidin-4-ylamino)piperidin-1-yl)-3-oxopropanenitrile 390 201130835

According to the experimental procedure as described in Example 46, from (3))-2-(6-fluoroimidazo[1,2-"]pyrene to 11--3-yl)-7\^-(派咬-3 -yl)-6-(17/-1,2,4-dioxan-1-yl)pyrimidin-4-amine (61 mg, 0.16 mmol, preparation 74b) and 3-[(2,5- Bis-oxo-pyridin-1-yloxy]-3-oxo-propanenitrile (44 mg, 0.24 mmol, prepared as described in BE 875 054 (A1)) gave a white solid (45%). Purification by flash chromatography (dioxane to 9:1 dichloromethane / methanol). LRMS (m/z): 447 (M+l)+.]H NMR δ (CDC13): 0.87 (m) , 1H), 1.18 - 1.41 (m, 3 H), 1.74 - 2.08 (m, 2H), 2.18 (m, lH), 3.30 - 3.69 (m, 2H), 3.83 (m, 1H), 4.32 (d, 1H), 5.25 - 5.53 (m, 1H), 6.71 - 6.84 (m, 1H), 7.20 - 7.38 (m, 1H), 7.66 - 7.84 (m, 1H), 8.13 (bs, 1H), 8.51 - 8.69 ( m,1H), 9.22 (s,1H), 9.74 (d, 1H). Example 165 (i?)-3-(3-(2_(6-fluoroimidazo[1,2-ίΐ]pyridine-3- Base)-6-(4-methylpiperazin-1_yl) mouth bite-4-ylamino) trace bit-1-yl)-3-lateral oxypropyl guess 391 201130835

According to the experimental procedure as described in Example 46, @)-2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-6-(4-mercaptopiperazin-1-yl - Λ4 piperidin-3-yl)pyrimidine-4-amine (55 mg, 0.13 mmol, preparation 75b) and 3-[(2,5-di- oxetidin-1-yl)oxy A 3-sided oxypropionitrile (37 mg, 0.20 mmol, prepared as described in BE 875 054 (A1)) afforded a white solid (75%), followed by flash chromatography (dichloromethane to 8: 2 dichloromethane / methanol) purified. LRMS (m/z): 478 (M+l)+. !H NMR δ (CDC13): 1.53 - 1.89 (m, 5H), 1.96 (m, 1H), 2.15 (ddd, 1H), 2.37 (s, 3H), 2.54 (t, 4H), 2.97 (d, 1H ), 3.28 - 3.37 (m, 1H), 3.43 - 3.52 (m, 1H), 3.64 - 3.74 (m, 4H), 4.08 (d, 1H), 4.50 - 4.73 (m, 1H), 5.48 (d, 1H ), 7.21 (dddd, 1H), 7.66 (td, 1H), 8.45 (d, 1H), 9.81 (ddd, 1H). Example 166 (Λ)-3·(3·(2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-6-(piperazin-1-yl) mouth bite-4- Amino group) brigade bit-1-yl)-3-sideoxycyan guess 392 201130835

Add /carbon (10%, 36 mg) to (Χ)-4-(6-(1·(2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoro) Imidazo[l,2-a]tf-pyridin-3-yl)pyrimidin-4-yl)piperazine_ι-methyl benzoate (204 mg, 0.34 mmol), 76 sterols (2 制备) The resulting mixture was stirred for 3 days in a solution of HCl) under hydrogen pressure (3 Torr/q2). The catalyst was then filtered and the solvent was removed by evaporation under a real coffee. By flash chromatography (2 MPa to 8:2) The title compound was obtained as a white solid. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ;H-NMR δ (DMSO-,6): (m? 4H)j 2 6.3 2 (m&gt; ϋ (m, 4H), 3.9_4 丨 (4) 2H), 4 * (d, $ H〇am), 7.5 (m,1H),7·8 (m,1H),8 Example 167 (and)-3-(3-(2-(6-fluoroimidazolyl)) Amine-encoded j-bit each base) o-(methyl-thylamino)piperidin-1·yl)-3-oxo-propanonitrile 393 201130835

Add triethylamine (20 μl, 0.14 mmol) and sulfonium chloride (9 μL, 0.12 mmol) to (Λ)-3-(3-(2-(6-fluoroimidazo[ 1,2-α] π ratio σ -3-yl)-6-(ΒΒ秦-1-yl) shouting ̄-4-ylamino)pyrazine-1-yl)-3-side oxygen The resulting mixture was stirred overnight at room temperature in a solution of dipropanenitrile (42 mg, 0.09 mmol, </RTI> 166). The reaction mixture was then diluted with methylene methane and the organic solvent was washed with water and brine, dried over magnesium sulfate and evaporated. The crude product was purified by flash chromatography eluting elut elut elut elut elut LRMS (m/z): 542 (M+l)+. H-NMR δ (CDC13): 1.7-2.2 (m, 4H), 2.8 (d, 2H), 3.0 (bs, 1H), 3.3-3.9 (m, 8H), 4.1-4.8 (m, 2H), 5.5 (d, 1H), 7.2 (m, 1H), 7.7 (m, 1H), 8.4 (d, 1H), 9.8 (m, 1H). Example 168 (i?)-3-(3-(2-(6-fluoroimidazo[1&quot;bipyridin-3-yl)-6-(N_morpholinyl))) -1-yl)-3-lateral oxypropyl 394 201130835

According to the experimental procedure as described in Example 46, by (external 2_(6_ 味峻和[1,2♦比咬-3-基)·6·(Ν•吗琳基)#(旅咬_3• Base _4 amine (68 mg '0.17 mM' preparation 77b) and 3_[(2,5-di- oxy-oxyl ratio)-oxyl-propanenitrile (47 mg, 〇26 mmol, prepared as described in BE 875054 (A1)) gave a white solid (44 〇 / 〇), followed by flash chromatography (di-methane to 9:1 di-methane/methanol) Purification. LRMS (m/z): 465 (M+l) + 〇lR NMR δ (CDC13): 1.58 - 1.90 (m, 2H), 1.91 - 2.03 (m, 1H), 2.15 (dd, 1H), 2.88 - 3.04 (m,1H), 3.17 (d,1H), 3.26 - 3.42 (m,2H), 3.43 · 3.73 (m,5H), 3.78 - 3.89 (m,4H), 4.03 - 4.18 (m, 1H) , 4.39 - 4.60 (m, 1H), 4.60 - 4.83 (m, 1H), 5.48 (d, 1H), 7.21 (dq, 1H), 7.66 (ddd, 1H), 8.45 (d, 1H), 9.80 (ddd , 1H). Example 169 CR)-3-(3-(6-(dimethylamino)·2_(6•fluoroimidazo[12_中比pyridineyl)) bite-4_ylamino) trace Acridine small base)_3_sideoxypropionitrile 395 201130835

According to the experimental procedure as described in Example 46, from (7?)-2-(6-fluoroimidazo[1,2-α]σ than indol-3-yldimethyl-_/V^ (Brigade bite -3-yl) mouth bite-4,6-diamine (46 mg, 0.13 mmol, preparation 78b) and 3-[(2,5-di- oxetidin-1-yl)oxy] -3-Sideoxypropionitrile (35 mg, 0.19 mmol, prepared as described in BE 875054 (A1)) afforded a white solid (75%), followed by flash chromatography (2 m. Purification of chlorodecane/furfuryl alcohol. LRMS (m/z): 423 (M+l)+.]H NMR δ (CDC13): 1.58 (s, 6H), 1.64 - 1.89 (m, 2H), 1.91 - 2.02 (m, 1H), 2.06 - 2.25 (m, 2H), 2.85 - 2.97 (m, 1H), 3.26 - 3.43 (m, 1H), 3.48 - 3.84 (m, 2H), 4.10 (bs, 1H), 4.39 - 4.71 (m, 1H), 5.26 - 5.37 (m, 1H), 5.39 (s, 1H), 7.20 (dddd, 1H), 7.66 (td, 1H), 8.46 (d, 1H), 9.93 (ddd, 1H) ° Example 170 (/0-3-(3 gas 2_(6-fluoroimidazo[l,2-fl]pyridin-3-yl)-6-(2-(N-morpholinyl)ethylamino)) Pyrimidin-4-ylamino) piperidinyl-1 -yl)-3-oxopropiononitrile

201130835 according to the experimental procedure as described in Example 46, from 〇R)-2-(6-fluoroimidazo[1,2-ίζ]π than 唆-3-yl)-7V^-(2-(N&quot; - 吓 基) ethyl)-A^-(唆唆-3-yl) pyrimidine-4,6-diamine (45 mg, 0.10 mmol, preparation 7%) and 3-[(2,5- Bis-oxyxyrrolidin-1-yl)oxy]-3-oxo-propanenitrile (28 mg, 0.15 mmol, as described in ΒΕ 875 054 (Α1)) afforded a pale yellow solid (77%) It was then purified by flash chromatography (dioxane to 88:12 dioxane / methanol). LRMS (m/z): 508 (M+l)+. !H NMR δ (CDC13): 1.55 - 2.05 (m, 4H), 2.10 - 2.25 (m, 1H), 2.46 - 2.60 (m, 4H), 2.67 (t, 1H), 2.81 - 3.04 (m, 1H) , 3.31 (ddd, 1H), 3.36 - 3.50 (m, 2H), 3.55 (s, 2H), 3.77 (d, 6H), 4.41 - 4.80 (m, 2H), 5.26 - 5.35 (m, 1H), 5.38 (s, 1H), 7.12 - 7.25 (m, 1H), 7.66 (td, 1H), 8.46 (d, 1H), 9.92 (d, 1H). Example 171 (and)_3_(3_(2-(6-fluoroimidazo[l,2-ii]~pyridin-3-yl)-6-(2-methoxyethylamino)pyrimidin-4-ylamino Piperidin-1-yl)-3-oxopropiononitrile

397 201130835 according to the experimental procedure as described in Example 46, from (and), 2 and [1,2·α]pyridine_3_yl)_#_(2_曱oxyethyl (piperidine (6, fluorine) Imidazole-4,6-diamine (123 mg, 〇32 mmol, preparation of soup), cardio)pyrimidine, 2-oxopyrrolidin-1-yl)oxy]-3-oxo-propanonitrile (87 3 , [(2,5, millimolar, as prepared in ΒΕ875〇54 (Α1)) obtained 彳θg, 〇.(68%)' then purified by flash chromatography (diqi methane to white Solid alkane/methanol): 1 digas 曱LRMS (m/z): 453 (M+l)+. iH-NMR δ (DMSO〇: 1.4-2.0 (claw, 4Η) 2 2H), 3.3 (d, 2H), 3.3 (s, 3H), 3.4-3.7 (m, 2H)', 35, 3a (m, 2H), 4.5 (bs, 1H), 5.4 (m, 1H), 6.8 (dd, (gong, 1H), 7.8 (m, 1H), 8.4 (d, 1H), 10.1 (s, m). ' lH), 7.5 Example 172 (5)· 1 -(6-((External 1 -(2-cyano) Ethyl hydrazide) piperidine _3_ylamine fluoroimidazo[1,2 pyridine pyridine-3-yl)pyrimidin-4-yl)pyrrolidine

According to the experimental procedure as described in Example 46, imiprazole-2 was obtained from indolo[1,2-α]pyridin-3-yl)-6-((8)-pyridinyl-3-ylamino). - formic acid (30 mg '〇.〇7 mmol, preparation 82c) and 398 201130835 di-side oxy σ-pyridin-1-yl)oxy]-3-oxo-propanonitrile (19 mg, 0.10 mM) Moore, prepared as described in BE 875054 (A1)) gave a white solid (58%), followed by reverse phase chromatography (from Waters C-18 cerium oxide, water/1:1 acetonitrile-nonyl alcohol) Purified as a dissolving agent [0% to 100% by 0.1% v/v citric acid buffer). LRMS (m/z): 493 (M+l)+. !H NMR δ (DMSO-i/6): 1.41 - 1.65 (m, 2H), 1.70 - 1.84 (m, 1H), 1.94 - 2.11 (m, 4H), 2.20 - 2.37 (m, 2H), 2.89 - 3.81 (m, 8H), 4.06 (d, 1H), 4.50 - 4.68 (m, 1H), 5.29 - 5.56 (m, 1H), 6.87 - 7.00 (m, 1H), 7.48 (m, 1H), 7.75 ( m, 1H), 8.35 -8.45 (m, 1H), 9.94 (bs, 1H). Example 173 (Λ)-3·(3-(2-(6-fluoroimidazo[l,2-ii]acridin-3-yl)-6-methoxypyrimidin-4-ylamino) brigade bite -1_基)-3-lateral oxycaline

According to the experimental procedure as described in Example 46, from (7?)-2-(6-fluoroimidazo[1,2-ίϊ]π than 唆-3-yl)-6-methoxyl (Broad Bite_3 _ base) shout bite -4 -amine (9 mg, 0.26 mmol, preparation 83b) and 3-[(2,5-di-oxypyrrolidin-1-yl)oxy]-3- side Oxypropionitrile (72 mg, 0.40 mmol, prepared as described in BE 875 054 (A1)) afforded a white solid (48%), followed by flash chromatography (dichloromethane to 95:5) Methane/sterol) and reverse phase chromatography (from Waters C-18 cerium oxide, water/1:1 acetonitrile-methanol as eliminator [0.1% v/v formic acid buffer] 0% to 1 〇〇 〇/〇) Purification. LRMS (m/z): 410 (M+l)+. , HNMRS (CDC13): 1.67 - 2.02 (m, 6H), 2.07 - 2.24 (square, 2H), 3.10 (dd, 2H), 3.29 - 3.50 (m, 4H), 3.52 - 3.67 (m, 4H), 3.69 - 3.79 (m, 2H), 3.86 (d, 1H), 4.03 (s, 3H), 4.06 (s) 3H), 4.42 (d, 1H), 4.82 (dd, 2H), 5.64 (d, 2H), 7.17 - 7.33 (m, 2H), 7.69 (td, 2H), 8.52 (d, 2H), 9.77 - 9.95 (m, 2H). 'Example 174 (J?)-3-(3-(2-(6-fluoroimidazo[1,2-ii]" than pyridine_3_yl)_6_(2 decapyridin-1·yl) B Oxy)pyrimidin-4-ylamino)piperidinyl)_3_sideoxypropionitrile

According to the experimental procedure as described in Example 46, by (Λ)_2_(6_fluoroimidazole [I, 2 比 啶 · 3 3 3 ) 旅 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Ethyl)pyrimidine_4_amine (mg mg, 0.26 mmol, preparation of 84 〇 and 3_[(2,5-di-oxyxyrrolidin-1-yl)oxy]-3- The side oxypropionitrile (71 mg, 0 40 mmol, as described in ΒΕ 875054 (Α1)) gave a white solid (58%), followed by flash chromatography (di-methane to 31 methylene chloride/methanol) Purification. 400 201130835 LRMS (m/z): 493 (M+l)+., H NMR 6 (CDCls): 1.77 (d, 6H), 1.95 - 2.32 (m, 2H), 2.56 - 2.83 (m, 4H), 2.98 (t, 2H), 3.12 - 3.50 (m, 3.50 - 3.80 (m, 2H), 3.80 - 4.11 (m, 1H), 4.30 (bs, 1H), 4.49 - 4.67 (m, 2H), 4.98 (d, 1H), 5.12 (bs, 1H), 5.69 (s^ 13⁄4 7.14 . 7.30 (m, 1H), 7.68 (dt, 1H), 8.49 (s, 1H), 9.65 - 9 92 (m 1H) v, Example 175 (Λ)-3-(3-(2-(6-fluoroimidazo[l,2·indolyl]_3_yl)_6·(2(Ν_Mallinyl)ethoxy)pyrimidine -4-ylamino) brityl-1_yl)_3_ pendant oxypropionitrile

According to the experimental procedure as described in Example 46, by (magic _2_(6·fluoroimidazo[1,2 rushing than 唆Q4-amine (1〇2 mg, 〇.23 mmol, preparation of Na) And 3_[(2,5_di-oxyl 比 唆 唆 )) oxy]_3_ oxopropanenitrile (63 mg, 〇35 mM, as described in ΒΕ 875054 (Α1)) (iv) white The solid (76%) was purified by flash chromatography (2H to hexanes: hexanes: MeOH): RMS (m/z): 509 (M+l) + 401 201130835 ^-NMR δ (CDC13): 1.7-2.2 (m, 4H), 2.6 (m, 4H), 2.8 (q, 2H), 3.3-3.6 (m, 4H), 3.7 (m, 4H), 3.8-4.0 (m, 1H) ), 4.4 (dd, 1H), 4.6 (q, 2H), 4.8 (d, 1H), 5.6 (d, 1H), 7.2 (m, 2H), 7.7 (m, 1H), 8.5 (d, 1H) , 9.8 (m, 1H). Example 176 〇Κ)·3_(3-(2·(6-fluoroimidazo[l,2-fl]acridin-3-yl)-6-(2-methoxy B Oxygen) cancer bit -4-ylamino) brigade-1-yl)-3-lateral oxypropyl

According to the experimental procedure as described in Example 46, (X-fluoro-2-(6-fluoroimidazo[1,2-α]«pyridin-3-yl)-6-(2-decyloxyethoxy) ) -7V-(piperidin-3-yl)pyrimidine-4-amine (62 mg, 0.16 mmol, preparation 86b) and 3-[(2,5-di- oxy-oxyl ratio) Oxy]-3-oxo-propanoid (44 mg '0.24 mmol, prepared as described in BE 875054 (A1)) afforded a white solid (62%), followed by flash chromatography (dichloromethane) Purification to 9:1 dioxane/sterol) LRMS (m/z): 454 (M+l) +. NMR δ (CDC13): 1.7-2.2 (m, 4H), 3.1-4.1 ( m, 11H), 4.3-4.6 (m, 2H), 4.9 (d, 1H), 5.7 (s, 1H), 7.2 (m, 1H), 7.7 (m, 1H), 8.5 (m, 1H), 9.8 (m, 1H). 402 201130835 Example 177 (External 6-(1-(2-cyanoethyl)-branches _3· and [1,2-&lt;1]咐i--3-yl) mouth Acridine·4 carbonitrile

Aminoamino)-2-(6-fluoroflavored saliva according to the experimental procedure as described in Example 46 and [1,2♦ than pyridine-3-yl) Yangchen an external oxazole η 9^^ π - J Ux pyridine-3_ylamino)pyrimidine-4·carbonitrile (77 y J yield 87) and hydrazine (2,5-di-oxyl, each bite) _ yl)oxy]--side oxygen Alkylpropionitrile (a mg, Ο% mmol, prepared as described in BE 875054 (A1)) gave a white solid (%%) followed by flash chromatography (di-methane to 9:1 dichloromethane / hydr. Alcohol) purification. LRMS (m/z): 405 (M+l)+. 1η NMR δ (CDC13): 1.67 - 2.23 (m, 4H), 3.36 - 3.82 (m, 5H), 3.85 - 4.12 (m, 1H), 4.23 - 4.59 (m, 1H), 5.75 (d, 1H), 6.54 - 6.77 (m, 1H), 7.29 (d, 1H), 7.69 (dd, 1H), 8.42 - 8.69 (m, 1H), 9.76 (bs, 1H). Example 178 (J?)-3-(3-(2-(6-fluoroimidazo[l,2-fl]acridin-3-yl)·6-(2ίΓ_tetrazol-5-yl)pyrimidine-4 -ylamino)piperidin-1-yl)-3-oxopropiononitrile 403 201130835

According to the experimental procedure as described in Example 46, (and)_2_(6-fluoroimidazo[1,2-α]pyridin-3-yl)-λα-(piperidine-3-yl)·6·( 2 private tetrazole _5•yl)pyrimidine-4-amine (54 mg '0.14 mmol, preparation 88) and 3_[(2,5 di-oxo-oxazolidine-1-yl)oxy]_3 _Phenoxypropionitrile (66 mg, 〇% mmol) as described in ΒΕ 875054 (Α1) gave a white solid (33%), after ρ by reverse phase chromatography (from Waters C18 dioxo, water / 1:1 acetonitrile-methanol as a dissolving agent [via 1.1% v/v citrate buffer] 〇% to 1%)). LRMS (m/z): 448 (M+l)+. 4 NMR δ (DMSO- 145 _ i 71 (m, 3H), ( 73 _ i 87 (m, 1H), 2.00 - 2.14 (m, 1H), 2.78 2.88 (m, 1H), 3.59 (d, 1H) ), 3.71 (d, 1H), 3.85 - 4.04 (m&gt; ih), 4.09 (d, 1H), 4.22 - 4.37 (m, 1H), 4.55 (d, 1H), 7.24 (d, 1H), 7.58 ( Td, 1H), 7.84 (dd, 1H), 7.99 - 8.11 (m, 1H), 8.66 - 8.78 (m, 1H) 9 92 -10.07 (m,lH). 'Instance 179 (Λ)-3-(3 -(2-(6-fluoroisoxazole 丨1&gt;2•中比pyridineylmethyl•1仏tetrazole-5-yl)pyrimidin-4-ylamino)piperidinyl)_3_sideoxy Propionitrile 404 201130835

According to the experimental procedure as described in Example 46, (/?)-2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-6-(1-indolyl-indole/f -tetrazol-5-yl)-dos(piperidin-3-yl)pyrimidin-4-amine (48 mg, 0.12 mmol, preparation 90) and 3-[(2,5-di- oxy oxime) <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; The crude product was triturated with chloroform and the insoluble solid was filtered, washed with hexane and dried. LRMS (m/z): 462 (M+l)+. ^-NMR δ (CDC13): 1.6-2.2 (m, 4H), 2.5 (s, 3H), 3.3-3.7 (m, 4H), 4.4 (m, 1H), 4.6 (d, 2H), 7.3 (m , 3H), 7.7 (m, 1H), 8.5 (d, 1H), 9.8 (s, 1H). Example 180 (and)-3-(3-(2-(6-fluoroimidazo[1,2-α]pyridin-3-yl)-6·(2-methyl-2Η-tetrazol-5-yl) Pyrimidin-4-ylamino)piperidin-1-yl)-3-oxopropanenitrile 405 201130835

• according to the experimental procedure as described in Example 46, by (Phantom-2-(6-fluoroimidazo[1,2-β]acridin-3-yl)-6-(2-mercapto-2// -tetrazol-5-yl)-7V-(piperidin-3-yl)pyrimidin-4-amine (40 mg, 0.10 mmol, preparation 91) and 3-[(2,5-di- oxy oxime) <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; ): 462 (M+l)+. ^-NMR δ (CDC13): 1.6-2.2 (m, 4H), 2.4 (s, 3H), 3.4-3.7 (m, 4H), 4.3 (m, 1H), 4.5 (d, 2H), 7.3 (d, 3H), 7.7 (m, 1H), 8.6 (m, 1H), 10.2 (d, 1H). Example 181 (Λ)-6-(1-(2-Cyanide) Ethyl hydrazide)piperidin-3-ylamino)-2-(6-fluoroimidazo[l,2-d]pyridin-3-yl)pyrimidine-4-carboxylic acid

406 201130835 According to the experimental procedure as described in Example 46, 〇R)-2-(6-fluoroimidazolyl)-6-(bunk-3-ylamino)carcinoma bite-4-decanoic acid (167 House, 0.47 mmol, Preparation 92b) and 3-[(2,5-di-oxypyrrolidin-1-yl)oxy]-3-oxo-propanenitrile (128 mg, 0.70 mmol) , prepared as described in BE 875054 (A1)) to obtain a white solid (35%), followed by reverse phase chromatography (from Waters C-18 cerium oxide, water / 1:1 acetonitrile-nonanol as dissolution) The agent [purified by 0.1% v/v citric acid buffer] 0% to 100%). LRMS (m/z): 424 (M+l)+. !H-NMR δ (DMSO-^): 1.2-2.1 (m, 4H), 3.2 (m, 2H), 3.6-4.6 (m, 4H), 7.0 (d, 1H), 7.5 (m, 1H), 7.8 (m, 1H), 8.6 (d, 1H), 10.2 (s, 1H). Example 182 (and)·6-(1·(2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[1,2-&lt;1]pyridine-3 -yl)pyrimidine-4-carboxamide

Will hydrate 1-hydroxybenzotriazole (24 mg, 0.18 mmol), (3-diaminopropyl)-W-ethylcarbodiimide hydrochloride (34 mg, 0.18 mmol) And concentrated aqueous ammonium hydroxide (12 μL, 0.3 mmol) added to (Fanta-6-(1-(2-cyanoethyl)piperidin-3-ylamino)-2-(6) -Flumir 407 201130835 201130835

Purified residue from Waters 〇18 二2 矽 'water/1:1 acetonitrile-methanol as [0.1% v/v citric acid buffer] 〇% to 100%), p, mg (74%) white The title compound is obtained as a solid. To 37 LRMS (m/z): 423 (M+l) + 〇*H-NMR δ (DMSO-c/6): 1.5-2.1 (m, 4H), 2.8-3 2 3H), 3.6-4.5 (m, 4H), 7.0 (m, 1H), 7.5 (m, 1H), 7 8.3 (S, lH), 8.8 (d, lH), 9.8 (m, 1H). 〖,), Example 183 -4-ylamino)piperidin-1-yl)_3_ pendant oxypropionitrile

-(6_It imidazo[l,2_ii]pyrozole·3_base) mouth bite

A white solid (33%) was obtained, which was purified by flash chromatography (dichlorobenzene to &lt;RTI ID=0.0&gt;&gt; LRMS (m/z): 395 (M+l)+. H-NMR δ (DMSO-^): 1.4-2.0 (m, 4H), 2.5-3.2 (m, 2H), 3.5-4.1 (m, 4H), 4.5 (bs, 1H), 5.4 (d, 1H) ), 6.4 (s, 2H), 6.8 (dd, 1H), 7.5 (m, 1H), 7.7 (m, 1H), 8.3 (d, 1H), 10.1 (s, 1H). Example 184 (/〇·3·(3·(5·1-2-(6-fluorothiazolo[l,2-ii]pyridin-3-yl)-6-(N-heptyl) spray咬-4-ylamino) pieto-1-yl)-3-lateral gas-based

According to the experimental procedure as described in Example 46, (Λ)-5-fluoro-2-(6-fluoroimidazo[1,2-indole-3-acridin-3-yl)-6-(N-morpholine ))-AK piperidinyl)pyrimidine-4-amine (80 mg, 0.19 mmol, preparation 95c) and 3-[(2,5-di- oxetyrridin-1-yl)oxy] -3-Sideoxypropionitrile (53 mg, 0.29 mmol, prepared as described in BE 875 054 (A1)) afforded a white solid (50%), followed by flash chromatography (dichloromethane to </ br> Alkane/sterol) purification. LRMS (m/z): 483 (M+l)+. !H-NMR δ (CDC13): 1.7-2.2 (m, 4H), 3.2-3.9 (m, 12H), 409 201130835 4.2 (m, 1H), 4.8 (m, 1H), 7.2 (m, 1H), 7.7 (m, 1H), 8 4 (m 1H), 9.7 (m, 1H). ' · ' Example 185 (Λ)-1-((/〇-3-(5-fluoro-2-(6-fluoroimi) is more than bite_3_yl)-6-(N-morphaki) Bite-4-ylamino group) Bite-1-base&gt;2,3_di-propyl-propion 1-嗣

According to the experimental procedure as described in Example 95, (and) 2,2-dimethyl-1,3-dioxolan-4-carboxylic acid (40 mg, 0.27 mmol) and w_5·fluoro- 2-(6-fluoroimipirin[1,2_ί3] &gt;» than -3-yl)-6-(N-morphinyl) good (Brigade bite _3·yl) mouth α定_4_amine (Milligrams, 0.18 mmol, Preparation 95c) afforded a white solid (41%), followed by acetic acid (120 ° C, 15 hr). By reverse phase chromatography (from Waters C-18 dioxide, water/ι: I acetonitrile-nonanol as eliminator [0.1% v/v formate buffer] 0% to 1 〇〇〇/ 0) Purification of the crude product. LRMS (m/z): 504 (M+l)+. ^-NMR δ (CDC13): 1.7-2.1 (m, 4H), 3.4-3.9 (m, 15H), 4.2-4.6 (m, 2H), 5.1 (m, 1H), 7.2 (m, 1H), 7.7 (dd, 1H), 8.4 (m, 1H), 9.7 (m, 1H). 410 201130835 Example 186 5 (/0-3-(3-(2-(6-fluoroimidazolyl (10) is called pyro-(trimethylmethyl-4-amino)-Mt.

According to the experimental procedure as described in Example 46, from (external 2_(6_Fluoro miso[1,2-α]-hydroxy-3-yl) 曱 基-ΛΚ 幻 幻 ))_5_(三瓦甲Base 4-amine (80 mg, 0.19 mmol, preparation 97b) and 3 [(2,5-di-oxypyrrolidin-1-yl)oxy l·3-side oxypropionitrile (53 Kuitun, 029 millimolar, prepared as described in the lion (5) (obtained / white chrome solid (72%), followed by flash chromatography (two gas methane to 95:5 two gas institute / methanol) Purification. 'LRMS (m/z): 478 (M+l)+., HNMR5^^^-1.89^2^, 1.91-2.03 (m, 1H), 2.13 - 2.27 (m,1H), 3.14 ( Dd,1H),3.33 - 3 52 (m 4H), 3.67 (d, 1H), 3.82 (dd, 1H), 4.12 (s, 2H), '4 30 (d im 4.52 (cjd,1H),5.57 ( Bs, 1H), 7.30 (dd, m), 7 ' ' 8.64 (s, 1H), 9.60 - 9.80 (m, 1H) 〇, 'H), pharmacological activity, in vitro JAK kinase assay using the following instructions To characterize compounds for screening compounds for inhibition of Jaki 411 201130835 JAK2 and JAK3. Using the baculovirus expression system, human JAK1 (aa 850-1154), JAK2 (aa 826-1132), JAK3 (aa 795-1124) And Tyk2 (aa 871- The catalytic domain of 1187) appears as an N-terminal GST-fusion protein and is purchased from Carna Biosciences. The enzyme activity is determined using biotin-labeled poly(GT)-biotin (CisBio) as a substrate. The peptide concentration in the reaction is JAK1 is 60 nM, for JAK2 is 20 nM, for JAK3 is 140 nM and for Tyk2 is 50 nM. The degree of phosphorylation is detected by tjme_res〇ived fluorescence energy transfer (TR-FRET). Contains enzyme, ATP and peptide in 8 mM MOPS (pH 7.0), 1〇!!1]^]^(:12, 〇.〇5%0-mercaptoethanol, 〇.45 mg/ml] Each kinase in the mixture was measured for IC5 化合物 of the compound. The ATP concentration in the reaction was 3 μΜ for JAK1, 0.2 μΜ for JAK2, 0.6 μΜ for JAK3, and 8 μΜ for Tyk2. The enzymatic reaction was carried out at room temperature. minute. Next, use 20 μl of quenching detection buffer containing hydrazine, 115 μg/ml of phosphotyrosine phosphotide (ΡΤ66)-cryptate (CisBio) and variable concentration of SA-XL665 (CisBi〇). (50 mM HEPES, 0.5 M KF, EDTA 0.25 Μ, 0.1% (w/v) BSA, ρΗ7·5) The reaction was stopped to keep the sa_b ratio constant. The incubation was carried out for 3 hours and read on a Vict〇r 2V spectrofluorometer (PerkinElmer) set to read fluorescence resonance energy transfer. Some of the abbreviations used above have the following meanings: AA: Amino acid 412 201130835 GST: glutathione-S_transferase MOPS: 3·(Ν-morpholinyl)propanesulfonic acid BSA: Bovine serum white egg ΑΤΡ: Adenosine triphosphate EDTA: ethylenediaminetetraacetic acid HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Table 1 describes the IC50 values for certain exemplary compounds described in the present invention. In Table 1, "A" indicates that the IC50 value is less than 0.1 μΜ (ΙΟΟηΜ), and “Β” indicates that the IC50 value is in the range of 0.1 μΜ (100 ηΜ) to 1 μΜ (1000 ηΜ), and C indicates that the IC50 value is higher than 1 μΜ (1000 ηΜ). Table 1

Example number IC5〇JAK3 (μΜ) IC5〇JAK2 (μΜ) IC50JAKI (μΜ) 1 AAB 6 BBC 10 BAC 13 BBC 21 AAB 22 AAC 25 BBB 31 BAB 38 BAC 42 CBC 45 BBC 57 AAC 64 AAA 67 BAB 68 AAB 76 BAC 80 A 1 AA 82 CBC 89 CBC 413 201130835

Example Number &amp;JAK3 (μΜ) |lC^〇JAK2 (μΜ) | IC5〇 JAK1 TmMY

From the visible, the compound of formula (1) is the 卩 卩 axis of JAK BU JAK2 and JAK3 JAK1. Preferably, the derivative of the present invention inhibits the π% value of Κ2 and jaK3 kinase (as determined above, 'μΜ' is preferably less than 〇5 μΜ for each JAK kinase. Combination with inhibition (4) by inhibition. Combination of other active compounds to improve pathological conditions or diseases. Combinations of inventions may include - or a variety of other active agents known to be useful in the treatment of diseases: spinal proliferative disorders ( Such as true 414 201130835 dysplasia, essential thrombocythemia or myelofibrosis), leukemia, lymphoid malignant disease and physical dependence; bone and organ transplant rejection; immune-mediated diseases and inflammatory diseases, such as Zhao Zengqi Leukemia, lymphoid malignant disease, and solid axis; bone- and organ transplant rejection; and immune-mediated diseases; more specifically, wherein the pathological condition or disease is selected from rheumatoid arthritis, multiple sclerosis Symptoms, inflammatory bowel disease, dry eye, uveitis, allergic conjunctivitis, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis And psoriasis, such as: (a) dihydrofolate reductase inhibitors such as Methotrexate or CH-1504; (b) DHODH inhibitors such as leflunomide (leflunmide) , a compound described in teriflunomide or international patent application No. WO 〇 〇〇 8/〇 77 693 and WO 200900696; (c) an immunomodulator such as Glatiramer acetate (Copaxone), Laquinimod or Imiquimod; (d) DNA synthesis and repair inhibitors such as Mitoxantrone or cladribine ( Cladribine); anti-α4 integrin antibody such as Natalizumab (Tysabri); (f) α4 integrin antagonists such as R-1295, TBC-4746, CDP-323, ELND-002, non-pulling Firategrast or TMC-2003; (g) corticosteroids (3) rticoid and giaccocorticoid.-, such as prednisone or methylprednisolone, fluticasone, mo Metatasone or beta per pine (be Ta-metasone); (h) anti-butene 415 201130835 diacid ester, such as 10,000 G-/2; (i) anti-alpha antibody, such as infliximab, adalimumab Or Certolizumab pegol; (j) Soluble TNFα receptors, such as etanercept; (k) anti-CD20 monoclonal antibodies, such as Rituximab, Oak Mizumabum (〇creiizumab), ovamuumab (Ofatumumab) or TRU-015; (1) anti-CD52, such as alemtuzumab; (m) anti-CD25, such as daclizumab (daclizumab) ( η ) anti-CD88, such as eoilizumab or pexiHzumab; ( 〇) ^ IL12R/IL23R, such as ustekinumab; (p) | bow Calcineurin inhibitors, such as cyclosporine A or tacr〇limus; (q) iMpmj inhibitors such as chlorpyrifos acetate (myC〇phen〇) (a) cannabinoid receptor agonist, such as sartrifva (Sadvex); (s) chemokine CCR1 antagonist, such as MLN-3897 or PS-031291; (t) Factor CCR2 antagonists, such as incB-8696; (u) NF-κΒ activation inhibitors, such as MLN-0415; (v) SIP receptor agonists, such as fingolimod, BAF-312 or ACT128800; (w) S1P liase inhibitors, such as LX2931; (X) Syk inhibitors, such as R-112; (y) PKC inhibitors, such as NVP_AEB〇71; (z) M3 antagonists, such as tiotropium (ti〇tr〇pium) or acridinium; (aa) long-acting beta-adrenergic agonist, such as salmeterol (salmeterol), formoterol (f〇rm〇ter〇1 Or indacaterol; (bb) vitamin d derivatives such as calcipotriol 416 201130835 (calcipotriol) (Daivonex); (cc) phosphorus

Acid diesterase IV inhibitors such as r〇flumilast or GRC_4〇39; (dd) p38 inhibitors such as ARRY-797; (ee) MEK inhibitors such as ARRY-142886 or ARRY-438162 (ff) Ι^Κδγ inhibitor; (gg) interferon' including interferon beta la, such as Avonex from Bi〇gen Idee, CinnoVex from cinnaGen, and from Merck Serono Rebif, and interferon beta lb, such as Betaferon from Schering and Betaseron from Berlex; and (hh) interferon alpha, such as Sumiferon MP ° Specific examples of corticosteroids and glucocorticoids suitable for the combination of JAK inhibitors of the invention are prednisolone, methylprednisolone, dexamethasone (hasone), dexamethasone cipecilate, naf]ocort. , deflazacort, halopedone acetate, budesonide, beclomethasone dipropionate, hydrocortisone, triamcinolone Acetonide ), fluocinolone acetonide, fluocinonide, clocortolone pivalate, methylprednisolone aceponate, dexamethasone palmitoate, I tilpo Tipredane, hydrocortisone aceponate, prednicarbate, alclometasone dipropionate, halometasone, 417 201130835 (methylprednisolone suleptanate), mometasone furoate, rimexolone, prednisolone farnesylate, ciclesonide, budeco propionate (butixocort propionate ), RPR-106541, deprodone propionate, fluticasone propionate, fluticasone furoate, halobetasol propionate, gastropin (loteprednol etabonate), betamethasone butyrate (betamethasone bu) Tyrate propionate), flunisolide, prednisone, dexamethasone sodium phosphate, triamcinolone, betamethasone 17-valerate 'betamethasone (betamethasone), betamethasone dipropionate, hydrocortisone acetate, hydrocortisone sodium succinate, prednisolone sodium phosphate, and propylene butane Cortex_(hydrocortisone probutate). Specific examples of suitable Syk kinase inhibitors that can be combined with the JAK inhibitors of the invention are fosfamatinib (from Rigel), R-348 (from Rigei), R_343 (from Rigel), R-112 (from Rigel), piceatannol, 孓(2-aminoethylamino)-4-[3-(trifluoromethyl)anilino]pyrimidine _5. formamide, R-〇91 (from 1^61),6-[5-fluoro_2-(3,4,5-tridecyloxyanilino)pyrimidin-4-ylamino]-2,2-dimercapto-3,4-di Hydrogen-2H-acridino[3,2-b][l,4]oxazin-3-one besylate 418 201130835 (R-406 'from Rigel), l-(2,4,6-three Hydroxyphenyl)-2-(4-decyloxyphenyl)ethan-1-one, N-[4-[6-(cyclobutylamino)_instole_嗓呤j·ylamino]phenyl]- Ν-mercaptoacetamide (QAB-205 from Novartis), 2-[7-(3,4-dimethoxyphenyl) oxazolo[l,2_c]pyrimidin-5-ylamino]indole Acridine_3_carbamamine dihydrochloride (BAY-61-3606 from Bayer) and AVE-0950 (from Sanofi-Aventis). Examples of suitable m3 antagonists (anti-cholinergic agents) which can be combined with the JAK inhibitors of the present invention are ti〇tr〇pium salts, oxitropium salts, and flutropium (flutr 〇pium) salt, ipratropium salt, gyrium pyrr〇nium salt, trospium salt, revastatin (revatr〇pate), ipatomate ( Espatropate), 3-[2·hydroxy-2,2-bis(2-thienyl)ethyloxy]-l-(3-phenoxypropyl)-l-nitrogenbicyclo[2·2.2] octane Alkane salt (especially adidinium salt, more preferably acridinium bromide), 1-(2-phenylethyl)-3_(9H-0305.9-ylcarbonyloxy)_1 _Nitrogen bicyclo [2.2.2] octane salt, 2-sided oxanthene, 2,3,4-tetrahydroquinazoline-3-carboxylic acid internal-8-fluorenyl-8-azabicyclo[3.2 .1] Oct-3-yl ester salt (DAU-5884), 3-(4-benzylpiperazin-1-yl)-1-cyclobutyl-1-hydroxy-1-phenylpropanone (NPC- 14695), N-[l-(6-Aminopyridin-2-ylindenyl)piperidine-4-yl]_2(R)-[3,3-difluoro-1(8)-cyclopentyl]-2- Benzyl-2-phenylacetamide (J-104135), 2(R)-cyclopentyl-2-hydroxy-N-[l-[4(vS)-decylhexyl]piperidine·4-yl ]-2 -Phenylethyl hydrazine v amine (J-106366), 2(R)-cyclopentyl-2-hydroxy-indole [1-(4-mercapto-3-pentenylindole-pyridinyl)-2 -Phenylacetamide (J-104129), 1-[4-(2-aminoethyl) succinyl-1-yl]-2(R)-[3,3-difluorocyclopenta-1 ( R)-yl]-2-carbyl-2·phenylethyl 419 201130835 -1-one (Banyu-280634), Ν-[Ν-[2-[Ν-[1-(cyclohexylmethyl)) -3(R)-ylmethyl]amine-mercapto]ethyl]amine-mercaptomethyl]_3 3,3-triphenylpropanamide (Banyu CPTP), 2(8)-cyclopentyl-2-hydroxyl -2-Phenylacetic acid 4-(3·azabis% [3.1.0]hex-3-yl)-2-butane vinegar (Ranbaxy 364057), UCB-101333, Merck's OrM3, 7- Endo-(2-carbyl-2,2-propenylethoxycarbonyl)-9,9-dimethyl-3-oxy-9-oxotricyclo[3.3.1.0(2,4)] Decane salt, 7-(2,2-diphenylpropanyloxy)-7,9,9-trimethyl-3-oxa-9-nitrogen tricyclic [3.3.1.0*2,4* Strontium salt, 7-carbyl-7,9,9-tridecyl-3-oxa-9-gas tricyclic [3.3.1.0*2,4*]壬9-methyl-9H- -9-formate salt - all of which are in the form of their racemates, their enantiomers, their diastereomers and mixtures thereof, and as appropriate The condition is in the form of a pharmacologically compatible acid addition salt. Among the salts, a vapor, a desert, an iodide, and an oxime sulfonate are preferred. A specific example of a long-acting beta-adrenergic agonist (β2-agonist) which can be combined with the JAK inhibitor of the present invention is terbutaline sulphate or fumarate Eform〇ter〇1 fumarate, anti-butyl sulphate “formoterol fumarate”, bambuterol, procater〇1 hydrochloride, Sibenetide hydrochloride (sibenadet hydrochloride), mabuterol hydrochloride, albuterol sulphate, salbutamol sulphate, salmeterol xinafoate, carmoterol hydrochloride, Hydrochloride (R)_salbutamol ((R)_albuterol hydrochloride), levobutamol hydrochloride 420 201130835 (Levalbuterol hydrochloride/Levosalbutamol hydrochloride), hydrochloric acid (-)-salbutamol ((i)-saibutamol hydrochloride), tartaric acid (R,R)-formote Luo ((R,R)_Formoterol tartrate ), Arformoterol tartrate, sulphate Bedordrine sulphate, indacaterol, Trantinterol hydrochloride, AZD-3199, GSK-159802, GSK-5979 (H, GSK-678007, GSK-642444, GSK-961081, AR- C98955AA, Milveterol hydrochloride, BI-1744-CL, and the compounds described in International Patent Application No. WO2007A24898, WO2006/122788A1, WO2008/046598, and WO2008095720. Specific examples of suitable acid-filled diesterase iv inhibitors of the JAK inhibitor combination are benafentrine dimaleate, etazolate, denbufylline, and lo Rolipram, cipamfylline, zardaverine, arofylline, filaminast, tipelukast, tofestrol (tofimilast), 0 picamiilast, tolafentrine, mesopram, drotaverine hydrochloride, lirimilast, roflus special , cilomilast, oglemilast, apremilast, tetomilast, non-Minist, (R)-(+)-4_[2- (3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl]D-pyridyl (CDP-840), N-(3,5-di-gas-4-«pyridyl)- 2-[1-(4fluorophenylindenyl)_5_ 421 201130835 thiol hydrazide (GSK-842470), 9-(2-fluorobenzyl) -N6-methyl_2_(trifluoromethyl)adenine (NCS_613), N-(3,5·digas·4_pyridyl)_8_decyloxyquinoline-5-carbamamine (D_4418) , 3-[3_(cyclopentyloxy)_4.methoxybenzoinyl]-6•(ethylamino)_8-isopropyl-3-indole hydrazine hydrochloride (V-11294A), 6-[3 -(Ν,Ν-didecylamine fluorenyl) phenylsulfonic acid hydrazino-(3-decyloxyanilinyl)methylbenzyl quinolate _3_ decylamine hydrochloride (GSK-256066), 4-[6,7-diethoxy-2,3-bis(methyl)naphthalen-1-yl]succinyl(2-methoxyethyl)acridine-2(1H)-one (T-440 ), (1)-trans-2-[3'-[3-(N-cyclopropylaminoindenyl)_4_sideoxy{4·dihydro],8-dipyridin-1-yl]-3- Fluorobiphenyl*4-yl]cyclopropanoic acid (MK_〇873), CDC_8〇1, UK-5000 (U, BLX-914, 2 -methoxycarbonyl-4-cyano-4(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)cyclohexanone, cis [4-cyano-4_(3_ ring) Propyl methoxy-4-difluoromethoxyphenyl)cyclohexan-1-ol, GRC-4039, CDC-8 (H, 5(S)-[3-(cyclopentyloxy)-4- Methoxyphenyl]-3(S)-(3-mercaptobenzyl)piperidin-2-one (IPL-455903), 0N0-6126 (Eur Respir J 2003, 22 (Supp. 45): Abst 2557 And the JAK inhibitors of the present invention as claimed in International Patent Application Nos. W003/097613, WO2004/058729, WO 2005/049581, WO 2005/123693, and WO 2005/123692. An example of a suitable ρΐ3Κδγ inhibitor is 2-mercapto-2_[4-[3-mercapto-2-oxooxy, 8-(3-quinolinyl)-2,3-dihydro-1H- Imidazo[4,5-c]quinolin-1-yl]phenyl]propanenitrile (BEZ-235 from Novartis), CAL-101 (from Calistoga Pharmaceuticals) and oxime ethyl-:^, _[3-(3, 4,5-Trimethoxyanilino) 11-pyridyl[2,3-7]吼422 201130835 Pyridin-6-yl]thiourea (AEZS_126 from AeternaZentaris). The compounds of formula (1) and combinations thereof described herein are useful in the treatment of spinal disorders, leukemias, lymphoid malignancies, and solid tumors; bone marrow and g transplant rejection; immune-mediated diseases and inflammatory diseases such as spinal proliferative disorders , white disease, lymphoid malignant disease, and solid tumors; bone forging and H-nucleus rejection; and reduction of mediators with beneficial effects such as rheumatoid arthritis, multiple sclerosis, inflammatory Enteropathy (such as ulcerative colitis with Ron's disease), dry eye, uveitis, allergic conjunctivitis, allergic asthma, chronic obstructive pulmonary disease (C〇PD), ectopic dermatitis, and cowhide:. The compounds and combinations of formula (1) herein can also be used to treat inflammation ΦΦ in the disease. In the two-state sample towel 'the compound of formula (1) described herein and the combination can be used in the treatment of Si-like illness, , leukemia, lymphoid malignant disease, and physical care, the money is caused by inhibiting the individual's Janus aggression ίί In the two-state, the compounds of formula (1) described herein, and & can be used to treat bone marrow and organ transplant rejection; immune-mediated == disease, such as bone marrow and organ transplant rejection; and soil-free conductivity Diseases such as bone marrow and organ transplant rejection. The treatment of the singer is usually achieved by 11 (four) 杰 个体 个体 个体 个体. The compound of formula (1) and the group σ described in the nucleus can be used to inhibit the Janus kinase (JAK). The active compounds in the combination may be administered in the same pharmaceutical composition or in a different composition intended to be administered by the same or different routes, simultaneously, concomitantly or according to the order of 423 201130835. Live _ will (4) or the time is very close to the spot, or two active agents can be taken in the morning while other active agents are taken at a later date. Or in another program, one or two active agents = taken twice a day while other active agents are taken daily - times, simultaneously with each other, or separately. Preferably at least two and = all active agents will be taken simultaneously. Preferably at least two More preferably = will be administered as a mixture. Note is also directed to a combination of a compound described herein and a therapeutic agent for the treatment of a pathological condition or disease which is improved by MK. In particular, the pathological condition or disease is selected from the group consisting of a myeloproliferative disorder, a leukemia, a solid tumor, an osteophyte, and an organ transplant rejection; a sexually transmitted disease, such as a vertebral proliferative disorder, white blood, a pain, and a sexually transmitted disease. Entity _ ; bone _ ||Official transplantation excludes ^ and immune-mediated diseases. More specifically, pathological conditions or self-winding; 1 arthritis, multiple sclerosis, inflammatory bowel disease' = allergic conjunctivitis, Allergic rhinitis, asthma, slowness!, atopic dermatitis and psoriasis. &amp; Heart, the combination of products can be used to treat lymphatic malignant diseases of spinal proliferative diseases and solid tumors. Naskin kinase is achieved. In another state, immune-mediated treatment of bone marrow and organ transplant rejection, sputum, and inflammatory diseases such as bone marrow and organ transplantation 424 201130835 response 'and immune-mediated diseases' such as bone marrow and organ transplantation Rejection. Treatment of these diseases and conditions is usually achieved by inhibiting the Gena kinase (;ΑΚ) of the individual. The combination product can be used to inhibit the Janus kinase IJAK) ° The present invention also encompasses the compounds of the present invention and Use of a variety of other therapies - combinations thereof - for the manufacture of a formulation or agent for the treatment of such diseases. The present invention also provides a treatment that is easy to inhibit by Jena A method for improving a pathological condition or disease, in particular, wherein the pathological condition or disease is selected from the group consisting of a spinal proliferative disorder, a white disease, a lymphoid disease, and a disease. Bone_ and 11 official transplant rejection; immune diseases and inflammatory diseases such as spinal cord proliferative disorders, white blood 'lymphatic malignancies and solid tumors; bone marrow and organ transplant rejection' and immune-mediated turnover. The pathological condition or disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis dry eye, uveitis, allergic conjunctivitis, allergic rhinitis, 5 pancreatic intestines 4 = clotting (COPD), atopic skin Inflammation and psoriasis; the method comprising administering a therapeutically effective amount of a compound described herein in combination with one or more of: a therapeutic agent. In particular, the treatment is achieved by inhibiting the Janus kinase of the individual. u The invention also provides a method of inhibiting a Janus kinase in an individual in need thereof, comprising administering to the individual, a subject in need thereof, a therapeutically effective amount of a compound described herein and/or a plurality thereof Face treatment Qi =: 425 201130835. Depending on the nature of the condition to be treated, the active compound of the combination of the invention may be administered by any suitable route, for example, orally (in syrup, lozenge, capsule, buccal, controlled release formulation, rapid dissolution) Preparation (in the form of a preparation); topical (in the form of a cream, ointment, lotion, nasal spray or aerosol), by injection (subcutaneous, intradermal, intramuscular, intravenous, etc.) or by inhalation (dry powder) , solution, dispersion, etc.). The active compounds of the group &amp; (i.e., the oxime derivatives of the present invention) and other optionally active compounds may be co-administered in the same pharmaceutical composition or intended to be used by the same or different The routes are administered separately, simultaneously, concomitantly or sequentially in different compositions. One embodiment of the present invention consists of a kit of dispensing portions comprising the materials of the present invention and shouting derivatives and instructions for simultaneous, simultaneous, separate or heterozygous use with another active compound. The active compound is turned into a treatment for a proliferative disorder, a leukemia, a lymphoid malignant disease, and a solid tumor; a bone graft and a normal transplant rejection; an immune-mediated disease and an inflammatory disease such as a spinal proliferative disorder, leukemia, lymph Malignant diseases and solid tumors; bone marrow and organ transplant rejections and immune-mediated diseases, and more specifically, for the treatment of rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, dry eye, Uveitis, 'allergic conjunctivitis, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, and psoriasis. Another embodiment of the present invention consists of a package comprising the taste of the present invention and "what organism and another active compound, said activation 426 201130835 σ is suitable for the treatment of spinal proliferative and solid tumors. Bone marrow is a disease, white disease, lymphatic malignant disease; 5 brigade "Μ · organ transplant rejection; immune-mediated disease" such as spinal proliferative disorders, leukemia 1 heart [sick disease and solid tumors and immunity Mediated (four), and financial reaction, sexual arthritis, more than # special 疋 s, for the treatment of rheumatoid allergic conjunctival nasal inflammation: r dry eye, uveitis, (c (10)), different tilting ^ ^, /:, slow '_ Plug Pulmonary Disease Pharmaceutical Composition The upper age composition includes the compound of the present invention and a pharmaceutical diluent or carrier. The invention further comprises the step of providing a compound comprising the present invention together with a pharmaceutically acceptable release agent or carrier and/or a plurality of other therapeutic remedies for inhibiting the Janus kinase (ΜΚ). A pathological record or disease, such as the disease previously described. In order to treat a pharmaceutical composition for treating a pathology or disease easily by inhibiting the path of Janus kinase (JAK), 病理 = the pathological condition or disease is selected from the group consisting of ridge-derived disease = leukemia, library Mr and solid tumors; bone marrow and organ transplant rejection of anti-invasive diseases and inflammatory diseases, such as (four) proliferative disease, leukemia, lymphoid malignant disease, solid tumors, transplant rejection, and immune-mediated diseases, and more; Device 1 or disease is selected from rheumatoid arthritis, multiple tropism, inflammatory bowel disease, dry eye, uveitis, allergic conjunctivitis, 427 201130835 allergic rhinitis, asthma, chronic obstructive pulmonary disease (c〇 PD), atopic dermatitis and psoriasis. The invention also encompasses the use of the pharmaceutical compositions of the invention for the manufacture of a medicament for the treatment of such diseases. The pharmaceutical composition can be used to treat spinal proliferative disorders, leukemias, lymphoid malignancies, and solid tumors. In this aspect, the treatment is achieved by inhibiting the Genus kinase of the face. In another aspect, the 'pharmaceutical composition can be used to treat bone marrow and organ transplant rejection; immune-mediated diseases and inflammatory diseases such as bone marrow and organ transplant rejection; and immune-mediated diseases such as bone marrow and organ transplantation Rejection. These diseases, as well as the treatment of the rest, can be realized. The pharmaceutical composition can be used to inhibit Jena II to change ί: : : ί for the treatment of 'Yi treatment by inhibiting the Janus kinase (JAK) two == disease, in detail, where the disease = and the entity Tumor, bone test and organ transfer = lymphoid malignant disease and solid age bone marrow 2; = reaction; and immune-mediated diseases, and more plant rejection of inflammatory arthritis, multiple sclerosis, successful dry eye, Membrane r croup, chronic obstructive pulmonary disease (COPD), =, fuf nasal psoriasis The method comprises administering a therapeutically effective amount of 428 201130835 pharmaceutical composition. In particular, the treatment is achieved by inhibiting the Genus kinase of the individual. The invention also provides a method of inhibiting a Janus kinase in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a pharmaceutical composition as defined herein to an individual in need of such treatment. The present invention also provides a pharmaceutical composition comprising at least an imidazopyridinium of the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient together with a pharmaceutically acceptable excipient such as a carrier or a diluent ). The activity may range from 0.001% to 99% by weight of the composition, preferably from 1% to 90% by weight of the composition, depending on the nature of the formulation and whether it is further diluted prior to application. The composition of the composition is preferably suitable for oral, inhalation, topical, nasal, rectal, transdermal or injectable administration. The pharmaceutically acceptable excipients which are combined with the active compound or the salt of the compound to form the compositions of the present invention are themselves well known and the actual excipients used will depend on the method for which the compositions are intended. The composition for oral administration may be a tablet, a delayed tablet, a sublingual agent, a gel®, an inhaled gas, an inhalation solution, a dry powder inhaler or a liquid preparation (such as a mixture, _, In the form of a record or suspension), the form of the compound of the invention is contained in the form of a kilogram; the formulation can be prepared by methods well known in the art. The diluent which can be used in the preparation of the composition comprises (4) a diluent which is compatible with the active ingredient and, if necessary, a coloring agent or a flavoring agent or capsule preferably contains _1_3〇〇〇 mg, more preferably 〇51〇〇. A pharmaceutically acceptable salt or equivalent of a pharmaceutically acceptable salt thereof. 429 201130835 A liquid-like compound suitable for use with π can be in the form of n. The solution may be the active compound &lt; ^ water soluble in association with, for example, a saccharide-forming saccharide, including the insoluble active compound of the invention or its medicinal bis, together with a suspending or flavouring agent, in association with water. Further, the composition for parenteral injection may be soluble or may not be dry and soluble in the pyrogen-free 2 intestinal injection fluid. U, other suitable formulas, and compositions thereof may be in the form of ointments, creams or lotions; /f forms all of which contain the square filaments well known in the art of the present invention. The active ingredient or the equivalent amount of the active ingredient which is usually in the range of (10)·3_mg per day is pharmaceutically acceptable: two doses can be daily- or more, preferably 1 to 仏: The dosage form of the present invention is preferably in a unit dosage form and can be well known in the art of pharmacy: the pharmaceutical composition of the present invention can be administered as follows: 1 right box or a few 'such as capsules, cachets (cache or tablets) , each of which has the active ingredient of the first ingredient; powder or granule; in the aqueous liquid It body emulsion. The living or liquid emulsion or the water-in-oil liquid (-) di-shaped t can also be a bolus (b°lus) A paper-based sugar-polymeric formulation will generally consist of a compound or a salt in a liquid carrier containing a flavoring agent or a 430 201130835 colorant (eg, a suspension or solution of B, a crude oil, olive oil, glycerin or water). Any pharmaceutical carrier used when the composition is in the form of a lozenge is usually used to prepare solid talc, gelatin, gum arabic (f. Examples of carriers include magnesium stearate, and sucrose. / (acia), Stearic acid, starch, lactose can be used as a lozenge by one or more depending on the situation. In a suitable machine medium pressure = dispersant mixing is free = agent: delete, surfactant or ingredient to prepare." Silk type (such as powder or granules) active chamber molding mixture of inert liquid diluent compound The tablet may optionally be coated with a coating or a mark and may be slowly or controlledly released. When the composition is in the form of a capsule, any conventional encapsulation is suitable, for example, in hard gelatin. The above carrier is used in the capsule. When the composition is in the form of soft gelatin, it can be considered as any pharmaceutical carrier which usually prepares silk liquid/floating liquid, such as water-based gum (called ueous gum), cellulose, silicate. Or an oil, and incorporated into a soft gelatin capsule. The dry powder composition for local delivery to the lung by inhalation may, for example, be in the form of a gelatin capsule and a cartridge or a foaming agent such as a laminated aluminum foil. (blister) form for use in an inhaler or insufflator. Formulations / compounds containing a compound of the invention and powder suitable for powder base (carrier material) 431 201130835 (such as lactose or starch) Mixtures. Lactose is preferably used. Each capsule or cartridge may generally contain between 2 micrograms and 15 micrograms of each therapeutically active ingredient. The active ingredient may be provided without excipients. The device can be packaged by using a suitable inhaler device such as Genuair® (hereinafter referred to as Novolizer® SD2FL) as described in the following patent application: WO 97/000703, WO 03/000325, and WO 2006 /008207. The derivative compound for transfusion comprises a composition of the upper inhalation and further comprises a non-additive compound in the form of a solution or a liquid in an inert vehicle such as water. It is a combination of conventional excipients (buffers, antimicrobials, tonicity modifiers, and viscosity modifiers) and can be administered by nasal pump. Eight types of skin and percutaneous nemesis include f dissolves compared to = unit turnover, such as (d), or metered gas / gelatin = so that patients can be administered a single dose. Agent 荦: ί / σ = the amount of each active agent required for the fruit will be treated as a specific live disease's treated individual and the specific condition being treated or cited as the following example: Composition Example 1 100 mg 50,000 each were prepared according to the following formula: 432 201130835 3-((3 external 3_{[2_(6_fluoroisoxazo[1)2^pyridine_3_yl)pyrimidin-4-yl]amine} Capsules of 3-oxoxypropionitrile (active ingredient):

Procedure The above ingredients were sieved through a 60 mesh screen and loaded into a suitable mixer and filled into 5 inch gelatin capsules. Composition Example 2 50,000 pieces each containing 50 mg of 3-((from)-3][2_(6-fluoroimidazo[I,2♦pyridinyl-3-yl))]amino]} Lozenges of keto-1-yl)-3.Sideoxypropionitrile (active ingredient): Active ingredient - Microcrystalline cellulose ' 1.95-3⁄4^1 Spray dried®^!^ ----- - 9.95 kg of carboxymethyl starch 0.4 kg hardy 曰醯 曰醯 丁 二 二 酸 朦 ϋ ϋ 卜 卜 卜 卜 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ 所有 所有 所有 所有 所有 所有 所有 所有 所有Millimeter sieves were then compressed into 3 ounces of tablets in a suitable mixer + mixing for 20 minutes and using a 9 mm button flat bevelled punch. The tablet collapse 433 201130835 The solution time is about 3 minutes. Modifications that do not affect, alter, alter or modify the basic aspects of the compounds, combinations or pharmaceutical compositions are encompassed within the scope of the invention. [Simple diagram description] None [Main component symbol description] None 434

Claims (1)

201130835 VII Patent application for a compound of formula (I), or a pharmaceutically acceptable oxide or stereoisomer thereof, for the treatment of pathological conditions improved by: or disease: % (JanUSKmase, JAK) m is 〇 or an integer of 1 to 3; Z is an oxygen atom or a group Nr5; ^ and γ independently represent a nitrogen atom or at least one of _CR9 and Y represents a nitrogen atom; with X in a sheet ^, ^2 1, 仏 and heart each independently represent a hydrogen atom; a dentate atom, an I group; a straight or branched chain Ci_Q alkyl; ." block group, ci-c4 i wire; Ci_C4^ group; c3_c ' 2 C4 aryl group a group containing 5 groups, an early ring or a polycyclic ring c5_c14, a group of 5 to 14 hetero atoms selected from 〇, s, and N, containing at least one hetero atom selected from 0, S, and N, 5 435 201130835 u =C5_C9 aryl or heteroaryl directly bonded to a bicyclic group of a member group or a hetero group, a secret or heterocyclic group: = Γ: a hetero atom selected from 〇, s, and N; having at most 12 pairs Or an aza having up to 12 carbon atoms, wherein the alkenyl, alkynyl, dentate, alkyl, cyclo, cyclo, aryl, hetero, heterocyclyl, bicyclic, nitrogen a heterobicycloalkyl group and an aza-bicycloalkenyl group unsubstituted or substituted with one or more substituents selected from the substituents Ra' and the alkyl group is unsubstituted or substituted with one or more selected from Rb base Or Ri, R2, R; 3, R4 and R9 independently represent a _SRi3 group, a _s〇Ri3 group, a -s(o)2r13 group, a -s(o)2nr13r14 group, _NRi3S(〇) 2Ri4 group, -NR13S(0)2NR14 group, -〇R13 group, _c(〇)〇Ri3 group, -〇-c(o)R13 group, -c(〇HCH2)n_Rl3 group, _NRi3Ri4 a group, a QOHCHA-NRuRm group, a group or a -NR13C(〇)-(CH2)n-NR14R15 group, wherein each η is deuterium, bt2; or in the presence of two adjacent -CR9 groups, Two adjacent _CR9 groups and the carbon atom to which they are bonded optionally form a c5_Ci2 aryl group or a 4 to 12 membered heteroaryl group, a cycloalkyl group or a heterocyclic group, the heteroaryl group and the heterocyclic group containing at least a hetero atom selected from the group consisting of hydrazine, S and N, said aryl group, heteroaryl group, cycloalkyl group and heterocyclic group being unsubstituted or one or more selected from a halogen atom, a straight or branched chain CH: 6 An alkyl, monocyclic or polycyclic C5_Ci4 aryl group, a 5 to 14 membered heteroaryl group containing at least one hetero atom selected from the group consisting of ruthenium, S and N, or a hetero atom containing at least one hetero atom selected from the group consisting of ruthenium, s and N Substituted to 14 436 201130835 substituents of heterocyclic groups, The alkyl group, the aryl group, the heteroaryl group, and the heterocyclic group substituent are unsubstituted or/or plural selected from a dentate atom, a hydroxyl group, a cyano group, a linear or branched chain C1_C6 Substituted or substituted by a substituent of a Crc4 haloalkyl group; Rs represents a hydrogen atom, a straight or branched chain crc6 alkyl group, and the alkyl group optionally has one or more selected from the group consisting of a hydroxyl group, a cyano group, a Ci_C4 aldentyl group, CrC4 is substituted with a substituent of a decyl group, a C3_C1G cycloalkyl group, a strepyl group or a 6-membered saturated N-containing heterocyclic ring, or r5 represents _s(q)2Ri(j, _s(q)2NRi()Rii group a group, a _c(o) 〇r1() group, a _c(〇)_(CH2)n_RiQ group or a group; R6 and I each independently represent a hydrogen atom, or a linear or branched chain CrQ alkyl group, The alkyl group is optionally selected from one or more selected from the group consisting of a hydroxyl group, a cyano group, an alkane, a CrC4 group, a CrQ alkoxy group, a c-heart group, a 3·° 7 % alkyl group, a phenyl group or a 6-membered saturated group. Substituted by a substituent of the N heterocyclyl ring; Rs represents a hydrogen atom; a dentate atom; a cyano group; a linear alkyl group; a C2-C4 alkenyl group, an alkyne group; a Γ Γ amp &amp; mosquito chain C丨-C6 A WC C 2^, 14 haloalkyl; Cl hydroxyalkyl, _ (cvc6 alkyl MCi_C4 Alkoxy); C3 ring county; monocyclic or polycyclic C5_Cl4 aryl '· containing at least —; 5 to 14 members of the heteroatoms of s and N heteroatoms, 5 to 14 members, s, S and N Heterologous ring: two = C3-C7 heterocyclic alkyl fluorenyl groups of a nitrogen atom; a double "j hetero-heteroaryl group containing a single ring of diaryl f directly bonded to a 5 to 9 member ring or heterocyclic group. Or a heterocyclic group containing at least one selected from the group consisting of 0, S and '&quot; heterogeneous 437 201130835 aza-bicycloalkyl having up to 12 carbon atoms or aza-bicycloalkenyl having up to 12 carbon atoms Wherein the alkenyl, alkynyl, dentyl, hydroxyalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, heterocycloalkyl ketone, bicyclo, aza bicyclo The alkyl group and the aza-bicyclic dilute group are unsubstituted or one or more selected from the group consisting of Ra, -(QQ alkyl)-CN group or -(CrC4 alkyl)-C(0)NR,R,, Substituents of the group are substituted by 'wherein r, and R' are the same or different and are selected from a hydrogen atom and a straight or branched chain CrC4 alkyl group; and the alkyl group is unsubstituted or substituted with one or more substituents selected from Rb Substituted; or R8 represents a -SR13 group -SOR13 group, -S(0)2R13 group, -s(o)2nr13r14 group, _NR13S(〇)2R14 group, -NR13S(〇)2NR14 group, -or13 group, -c(o) Or13 group, -〇-c(o)r13 group, -C(0)-(CH2)n-R13 group, _NR13R14 group, •C(0)-(CH2)n-NR13R14 group, Νί113(:(0)·((:Η2)η_;Κ14 group or -NR13C(0)-(CH2)n-NR14R15 group, wherein η is 〇, 1 or 2, or Rs together with Rs and R5 The nitrogen atoms of the knot together form a 4 to 10 membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and which is a linear or branched chain CrQ alkyl group, a monocyclic or polycyclic CRCM aryl group, containing at least one a 5- to 14-membered heteroaryl group selected from the group consisting of a hetero atom of hydrazine, S, and N, a 5- to 14-membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S, and N, and a -SOR10 group ' _C (〇MCH2) n-Ri 〇 group = -C(O)-(CH2)n-NR10Ru group substituted, wherein each η is 〇, 1 or 2, wherein the alkyl group, the aryl group, the heteroaryl group and the heterocyclic group Substituting one or more substituents selected from a proton, a thiol, a cyano, a linear or a branched bond 438 201130835 or a CrC4 Substituting 'and wherein the alkyl group is unsubstituted or substituted with one or more substituents selected from a halogen atom, a trans group, a cyano group or a Cl_C4 haloalkyl group; the limitation is that when m is 0 B, 'R_8 is not Is a -SR13 group, a group, a -S(〇)2R13 group, a -S(0)2NRl3R14 group, a _NRi3S(〇)2Ri4 group, an NR13S(0)2NR14 group, an -OR13 group, 〇_c(〇)r13 group, 'NR13R14 group, _NRl3C(0)_(CH2)n_Ri4 group or •NR13C(0)-(CH2)n-NR14R15 group, wherein Ra is a halogen atom; cyano group ; a straight or branched chain ^^^6, the alkyl group is unsubstituted or substituted with one or more cyano groups; CrC4 haloalkyl, CrC4 hydroxyalkyl; Q-C7 cycloalkyl or a q-C7 cycloalkenyl group; a monocyclic or polycyclic CVCh aryl group which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a murine group; and contains at least one selected from the group consisting of ruthenium, S, and a 5- to 14-membered heteroaryl group of a hetero atom of N, which is unsubstituted or substituted with one or more substituents selected from a halogen atom or a cyano group; and contains at least one selected from the group consisting of 0, S, and N. 5 to 14 membered heterocyclic groups of a hetero atom; a group; -SOR10 group; -S(〇)2r1〇 group; _s(〇)2NRi〇Ri] group; -nr10s(o)2ru group NRl〇s(0)2NR]i group; _〇Ri〇 group; -C(O)〇R10 group; -C(〇)_CH2〇r〇 group; -C(O)-(CH2)nO-(CH2)pR10 group; -C( O)-(CH2)nO-(CH2)pO-R10 group; _〇_c(〇)Ri〇 group; -C(0)-(CH2)n-Ri〇 group; -NRwRm group; -QOHCHA-NRwRn group; _Ri〇c(〇)-(CH2)n_NRiiRi2 group 439 201130835 团; -c(crc4 alkylvQOHciyn-NRwi^ group; -NRwCXOHOHbVRn group or -NRioQOMCHlNRnR^ group, wherein each η Is an integer of 0 or 1矣5' and wherein p is an integer from 1 to 3; Rb is cyano; hydroxy; straight or branched chain CrC6 alkyl; crC4 functional group, C1-C4 alkyl group, C; -C7 nucleobase or c;?-C7 cycloaliphatic; monocyclic or polycyclic Q-Q4 aryl, said aryl being unsubstituted or substituted by one or more substituents selected from a halogen atom or a cyano group a 5 to 14 membered heteroaryl group containing at least one hetero atom selected from the group consisting of hydrazine, S and N, which is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group; Into a few 5 to 14 membered heterocyclic groups selected from the heteroatoms of 0, S and N; -SR10 group; -SOR1G group; _S(〇)2Ri. group; _s(〇)2N ^ ' group ;-NRwSahR&quot;group; _NRi〇s(〇)2NRii group; 七11 group; -C(O)OR10 group; yl·10-C(O)-(CH2)nO-(CH2)pR10 group 'C(0)-(CH2)n-0-(CH2)p〇-R1〇 group; _〇c(〇)Ri〇-C(O)-(CH2)n-R10 group· ' _NR10Rn group I -C(O)-(C¥L2)n-^Rl0Ru ; -R1〇C(〇)-(CH2)n-NRuR12 ^ group; -c(crC4 alkyl)2_c(0)_ (CH2)n_NRi〇Rii group; -NR10C(〇HCH2)n-R&quot; group or tear i〇c(〇)_(CH2)n_NRii heart group, wherein each η is 0 or an integer of 1 to 5, And where? is the work to ^ integer; &lt; Rio, Rn and R12 each independently represent a carbon atom, an aryl group, or a branched chain crc6 alkyl group, crc4 _ alkyl group, CrC6 hydroxyalkyl group, c 1 440 201130835 aerobic group, c3-c7 ring alkyl group, stupid Base, _ (CrC4 via a hospital-C(0)-(stupidyl), containing 2, 3 or 4 5 to 6 membered monocyclic heteroaryls selected from N, anthracene and ^ atoms, containing Bu 2 or 3 a 5- to 6-membered heterocyclic group selected from hetero atoms of oxygen and a nitrogen atom, a q-C7 heterocycloalkyl ketone group containing 2 or 3 nitrogen atoms, and a monocyclic C5_Q aryl or heteroaryl direct bond a bicyclic group having 5 to 6 membered cycloalkyl or heterocyclic groups containing 2 or 3 hetero atoms selected from oxygen and a nitrogen atom, said haloalkyl group, hydroxyalkane Alkyl, alkoxycarbonyl, cycloalkyl, phenyl, hydroxyalkyl-phenyl, heteroaryl, heterocyclyl, heterocycloalkyl ketone and bicyclo are unsubstituted or one or more selected from substituents a substituent of RC is substituted, and the alkyl group is unsubstituted or substituted with one or more substituents selected from the substituent Rd; Rc is a halogen atom, a thiol group, a cyano group, a linear or branched chain group, Crc4 Halogenated group, crc4 alkoxy, CVC 4 calcined, c3-c7 cycloalkyl 'phenyl, 5 to 6 membered monocyclic heteroaryl containing 1, 2 or 3 nitrogen atoms' containing 5 to 6 members of 1, 2 or 3 nitrogen atoms a cyclic group, or a c3-C7 heterocycloalkyl ketone group containing hydrazine, 2 or 3 nitrogen atoms, wherein the phenyl group is unsubstituted or substituted with one or more dentate atoms, and the heteroaryl group, The cyclo and heterocycloalkyl ketone groups are unsubstituted or substituted by one or more straight or branched chain CrC3 alkyl groups; Rd is cyano, CrC4 _alkyl 'CrC4 炫*oxy' Ci-C4 hydroxyalkyl , a C3-C7 cycloalkylphenyl group, a 5- to 6-membered monocyclic heteroaryl group having 1, 2 or 3 nitrogen atoms, a 5- to 6-membered heterocyclic group having 1, 2 or 3 nitrogen atoms, or a a C3-C7 heterocycloalkyl ketone group of 1, 2 or 3, which is unsubstituted or substituted by one or more dentate atoms, and said heteroaryl 441 201130835, heterocyclic group And the heterocycloalkyl ketone group is unsubstituted or substituted with a mono- or branched chain crc3 alkyl; the bonds R13, R14 and R15 each independently represent a hydrogen atom, a cyano group, a straight or branched chain Crc6 alkyl group, a Cl_c4-alkyl group , Ci_C4 burned base, melon ^ burnt base HCA alkoxy HCl_C 6 silk) _ (containing at least one 5- to 7-membered heterocyclic group selected from two: two heteroatoms) 'CrQ alkoxy group' crc7 % alkyl, monocyclic or polycyclic c5_c] 4 aryl, containing a 5 to 14 membered heteroaryl group of at least one hetero atom selected from 0, S and N or a 5 to 14 membered heterocyclic group containing a hetero atom of it and N, wherein the tooth is burned, warp, and burnt oxygen And the cycloalkyl, aryl, heteroaryl and heterocyclic groups are unsubstituted or selected from one or more selected from the group consisting of, and the filaments are optionally substituted with one or more substituents selected from Rb. [Available as described in the first paragraph of the patent application, wherein the atoms 1, ί2., :3, R4 and R9 each independently represent a hydrogen atom; the south alkynyl group: a c chain or a branched chain CrC6 Alkyl; CrC4 alkenyl; c-c4 cycloyl; 1 single 4-ring j CrC4 nacelle; CrClQ cyclofilament; C3-C10 S and N:=% (VCl4 aryl; containing at least one selected from 〇, 0 , S and ～, 5 to 14 membered heteroaryl; containing at least one 5- to 14-cyclo group selected from aryl or hetero-M f atoms; containing a monocyclic C5-C9 group, said hetero-bond A hetero atom H or a heterocyclic group bonded to a bicyclic ring of a 5- to 9-membered cycloalkyl or heterocyclic group containing at least one aza-bicyclic ring selected from the group consisting of ruthenium, S and iridium up to 12 pounds having up to 12 carbon atoms Alkyl or aza-bicycloalkenyl having a halogen atom, 442 201130835 wherein the alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle a base, a bicyclic group, an aza-bicycloalkyl group, and an aza-bicyclic fluorenyl group are unsubstituted or substituted with one or more substituents selected from the substituents Ra, and the alkyl group is unsubstituted or one or more Substituted for a substituent selected from Rb; Or broadening the meaning and ^ independently representing the group, ^~ group, -S(0)2R13 group, _s(〇)2nr13r14 group, _NR13s(〇)2R14 group, -nr13s(o 2nr14 group, -〇r13 group, _C(〇)〇Ri3 group, -〇-C(0)R13 group, -C(〇;H:CH2)n_Ri3 group, _NRi3Ri4 group, -C (0)-(CH2)n-NR13R14 group, _NRl3C(〇)_(CH2)n_Ri4 group or NK13C(C〇_(CH2)n-NR14R15 group, wherein each η is 〇, 1 or 2; or In the presence of two adjacent _CR9 groups, two adjacent _Cr9 groups and their bonded carbon atoms optionally form a C5_Ci2 aryl group or a 4 to 12 membered heteroaryl group, a cycloalkyl group or a heterocyclic group. a cyclic group, said heteroaryl group and said heterocyclic group containing at least one hetero atom selected from the group consisting of 0, s and N, said aryl group, heteroaryl group, cycloalkyl group and heterocyclic group being unsubstituted or subjected to one or more One selected from halogen original =, linear or branched Cl_c6 alkyl, monocyclic or polycyclic C5_Ci4 aryl, containing 5 to 14 membered heteroaryls of at least one hetero atom selected from hydrazine, s and N or containing at least one selected 5 to 14 members of the hetero atom of hydrazine, S and n, substituted with a substituent of the % group, wherein The alkyl group, the aryl group, the heteroaryl group, and the heterocyclic group substituent are unsubstituted or one or more selected from the group consisting of a dentate atom, a trans group, a cyano group, a linear or branched chain Cl- Substituted by a C6 alkyl group, or a substituent of a crc4 haloalkyl group; Rs represents a hydrogen atom, a linear or branched CVC6 alkyl group, and the alkyl group 443 201130835 optionally has one or more selected from the group consisting of a hydroxyl group, a cyano group, and a CrC4 halogen. Alkyl, Ci_Q, alkyl, CVCh) cycloalkyl, phenyl or 6-membered saturated n-heterocyclic ring-substituted substituent substituted 'or Rs represents -S(〇)2R1〇 group, _s(〇)2NRi〇 Ru group, -C(O)OR10 group, _C(0)_(CH2)n_Ri(} group or -C(O)-(CH2)n-NR10R„ group; R6 and R7 are each independently represented a hydrogen atom, or a linear or branched chain CrC6 alkyl group, which is optionally selected from one or more selected from the group consisting of a thiol group, a cyano group, a crc4 halogen group, a CrC4 group, a calcium group, an oxygen group, and a hydrazine group. 3-(^7 cycloalkyl, phenyl or 6-membered saturated N-heterocyclic ring-substituted substituent; R·8 represents a hydrogen atom, a halogen atom; a cyano group; a linear or branched alkyl group, C2-C4 Alkenyl; C2-C4 alkynyl; crc4-alkyl; Ci_c4 hydroxyalkyl, Q- Cio% alkyl, Q-Cio cycloaliphatic; monocyclic or polycyclic c5_c aryl; 55 to 4 membered heteroaryl containing at least one hetero atom selected from 0, S and N; containing at least one selected from 0 a 5- to 14-membered heterocyclic group of a hetero atom of S, and N; a bicyclic group containing a monocyclic ring (5-(: 9-filament or a aryl group directly bonded to a 5- to 9-membered cycloalkyl group or a heterocyclic group) Said heteroaryl or hetero ara containing at least one hetero atom selected from the group consisting of hydrazine, S and N; aza-bicycloalkyl having up to &amp; carbon atoms or having up to 12 dicycloalkenyl groups, ', &lt;• noisy _ wherein the alkenyl group, alkynyl group, _alkyl group, hydroxyalkyl group, cycloalkyl group, rare earth group, aryl group, heterofilament, heterocyclic group, bicyclo group, aza·bis group = and aza-bicycloalkenyl unsubstituted or substituted by one or more selected from the group consisting of Ra, alkyl)-CN groups or -(Cl_C4 alkyl)_C(0)NR,R" groups And wherein R' and R'' are the same or different and are selected from a hydrogen atom and a linear chain, 444 201130835 branched-chain CrC4 alkyl; and the alkyl group is unsubstituted or substituted with one or more substituents selected from Rb Substituted; or 118 represents a _sr13 group, a -sor13 group, a _s(〇)2r13 group, a -S(0)2NR13R14 group, a _NR13S(0)2R14 group, a _NRl3S(〇)2NR" group, - OR13 group, _C(0)0R13 group, _0_C(0)R US-C(〇HCH2)n-Rl3 group, i3Ri4 -C(0)-(CH2)n-NR13R14 group, -NR13C( 〇)-(CH2)n-R14 group or -NR13C(0)-(CH2)n-NR14R15 group 'where η is 〇, 1 or 2, or R8 together with & and the nitrogen atom to which Rs is bonded Forming a 4 to 10 membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and which is subjected to a linear or branched chain crce alkyl group, a cyclic or polycyclic C5_Ci4 aryl group; a 5 to 14 membered heteroaryl group having at least one hetero atom selected from the group consisting of ruthenium, S and N, containing at least one hetero atom selected from the group consisting of ruthenium, S and N ^ a base of the -SOR10 group ' _C(〇MCH2)n_Ri〇 group or a C(O)(CH2)n-NR10Rn group, wherein each n is 〇, ι or 2, wherein the green, aryl, And the heterocyclic group is unsubstituted or substituted by one or more substituents selected from a halogen atom, a trans group, a cyano group, a linear or branched bond, or a CrC4 haloalkyl group, and wherein Or substituted with - or a plurality of substituents selected from a functional atom, a minus, a cyano group or a haloalkyl group; the limitation is that when m is 〇, rs is not a _SRu group, a _s〇Ri3 group, S(〇)2r13 group, _s(0)2NRi3Ri4 group, diatom group, -NRl3S(0)2NRl4 group, _〇Ri3 group, _〇_c(〇)Ri3 group, -NR^ Rh group, _ΝΚιΑ〇)_(αί2)η·Κΐ4 group or 445 201130835 _NRi3C(0)-(CH2)n-NR14R15 group, wherein Ra is a halogen atom; cyano group; hydroxyl group; linear or branched chain CrC6 Alkyl; Crc4 dentate alkyl; crC4 hydroxyalkyl; C3- a C7 cycloalkyl or CVC7 cycloalkenyl group; a monocyclic or polycyclic c5-c14 aryl group which is unsubstituted or substituted with one or more halogen atoms; contains at least one selected from the group consisting of ruthenium, S and N 5 to 14 membered heteroaryl of a hetero atom; 5 to 14 membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S and N; -SRio group; -SOR10 group; -S(O)2R10 a group; _s(〇)2NRi〇Rii group; _NR10S(O)2Rn group; -NR10S(O)2NR„ group; _〇r1〇 group; -C(O)〇R10 group; -C(O)R10 group; _C(〇)_(CH2)n_Ri〇 group; _NR1〇Rn group; -CXOHCHA-NRioRu group; -NR^CXOHCHA-Rn group or -NR10C(〇HCH2) n-NRnR12 group, wherein each n is 〇, 1 or 2; Rb is cyano; crC4 dentate; CVC4 hydroxyalkyl; C3-C7 cycloalkyl or cvc: 7 cycloalkenyl; monocyclic or polycyclic a C5_Cl4 aryl group which is unsubstituted or substituted by one or more halogen atoms; a 5- to 14-membered heteroaryl group containing at least one hetero atom selected from 0, S and N; 5 to 14 membered heterocyclic groups of heteroatoms of S and N; _SRi 〇 group; -SOR 丨〇 group; -s(〇) 2r 〇 Group; _s(〇)2NR10Rn group; -NR^C^Rn group; _NRi〇s(〇)2NRii group; _〇Ri〇 group; "C(O)OR10 group; -〇-c( 〇)r1〇 group; _C(〇)-(.CH2)n_R10 group; -NR10RU group; _c(〇)-(CH2)n_NRi〇Rii group; -NRwCCOHCHA-R&quot; group or _NRi〇 c(〇) (CH2)n_NRuRl2 group, wherein η is 0, 1 or 2; 446 201130835 R10, Ru and R12 are each independently known or branched &lt;^6 alkyl, cvc4 self-burning A ^ atom 'cyano, linear alkoxy group, C3-C7 cycloalkyl, stupid base, ^ rC4 by burning base 'ci-c4 month S's eyebrow early 5 5 g-mesh or 5 to 6M of the 5 to 6M early ring heteroaryl nitrogen atom selected from N, anthracene and S heteroatoms, containing a ring or a hetero group The aryl or heterocyclic group having 5 to 6 benzyl group or a heterocyclic group contains 1, 2 or 3 nitrogen atoms, and the aryl group, the alkyl group, the phenyl group, the phenyl group and the hetero aryl group. a group, a heterocyclic group, and a bis-yl group are unsubstituted or substituted with one or more substituents selected from the substituent Rc, and the alkyl group is unsubstituted or substituted with or a plurality of substituents selected from the group consisting of substituents Rd ; ~ Rc is a halogen atom, a trans group, a cyano group, a linear or branched chain Ci_C6 alkyl group, a CrC: a 4-haloalkyl group, a CrC4 alkoxy group, a crC4 hydroxyalkyl group, a c3-c7 cycloalkyl group, a phenyl group, 5 to 6 membered monocyclic heteroaryl groups of 1, 2 or 3 nitrogen atoms - 5 to 6 membered heterocyclic groups containing 2 or 3 nitrogen atoms, or CrC7 heterocyclic ring containing i, 2 or 3 nitrogen atoms An alkyl ketone group which is unsubstituted or substituted with one or more halogen atoms, and The heteroaryl, heterocyclyl and heterocycloalkyl ketone groups are unsubstituted or substituted by one or more straight or branched C! - c 3 alkyl groups; Rd is cyano 'CrC4 _alkyl, QQ alkoxy Base, CrQ hydroxyalkyl 'C; 3-C7 cycloalkyl, phenyl, 5- to 6-membered monocyclic heteroaryl containing 1, 2 or 3 nitrogen atoms, containing 1, 2 or 3 nitrogen atoms a 5- to 6-membered heterocyclic group, or a CrC having 1, 2 or 3 nitrogen atoms; a heterocycloalkyl ketone group which is unsubstituted or substituted with one or more functional atom atoms, and the hetero Aromatic 447 201130835, a heterocyclic group and a heteroweiyl group are unsubstituted or substituted by a plurality of straight or branched chain CrC3 alkyl groups; =13, R14 and R15 each independently represent a hydrogen atom, a cyano group, a straight Bond or ^ Branched Cl-c6 alkyl, CrC4 (tetra), Ci_C4, oxycarbonyl, cvc7 ring, monocyclic or polycyclic C5_Ci4, containing at least one heteroatom selected from 0, S and N a 14-membered heteroaryl group, or a 5- to 14-membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S, and N, and the i-filament, the ship base, the silk county, the cycloalkyl group, and the aryl group Heteroaryl and hetero-J clothing are unsubstituted With one or more substituents selected from the substituents Ra and the burn-yl optionally substituted with - one or more of the substituents selected from Rb. 3. The compound for use as described in item i or item 2 of the patent application and 1M are the same or different and each represents a hydrogen atom, a halogen original H cyano group, a linear or branched chain Ci.c6 alkyl group or C1- C4 hydroxyalkyl; soil chain atom, dentate atom, thiol, aryl group, direct bond or branch A, i 2 Γ γ Γ, CrQ dentate group, CrC4 burnt group, C3_Cl 〇 ring burner heterocyclic group, C6- Ci〇 square base, 5 to the member of the mixed or branched chain c Wei unsubstituted hetero- ❹ 4 4 liver, or direct bond R, R" / 6 alkyl, minus, aryl or CrC4 alkoxy Substituted; its bond C r K^R'n is the same or different and each represents a hydrogen atom, a linear or branched chain CrC6 alkyl group, a CrQ tooth alkyl group or a Ci &lt;: 4 hydroxyalkyl; 448 201130835 chain etc table f ί atom, (d) atom, thiol, cyano, linear or branched (tetra), (d) via the courtyard or core burnt 7), or together with R8 and - form 5 to 9 members of the round money η # people's gas atoms are heteroatoms and the one or two nitrogen atoms are used as the 县 reading county peaks or contain - or two nitrogen atoms c (0) / member heteroaryl, {(9) from 'group' or - a q〇HCH2) n marriage &quot;R," group substitution 'where n is 〇, i or 2, R is not a hydrogen atom, or a straight chain or Branched chain CrC6 alkyl, = or aryl, and R" and "quote the same or different and each; represents a thousand, straight or branched chain CrC6 alkyl, CrC4 haloalkyl or CrC4 hydroxyalkyl; 尺6和R ? identical or different and each represents a hydrogen atom, a straight or branched chain CrC6 alkyl group, a Ci_C4 dentate alkyl group, a Ci_Q hydroxyalkyl group or a _(Ci_C4 alkyl)-Het-(CrC4 alkyl group); the rule 9 is a hydrogen atom, Halogen atom, hydroxyl group, cyano group, linear or branched chain 1 C6 alkyl group, crc4 courtyardoxy group, crC4 halogen group, crc4 alkyl group, C3j7 ring hospital group, 5 to 10 member heterocyclic group or 5 to 10 members a heteroaryl group, the heterocyclic group The heteroaryl group is unsubstituted or substituted by one or more functional atom, or a linear or branched chain CrC6 alkyl, cyano, hydroxy, carboxy or crc4 alkoxy substituent, or R·9 is -Het-R ', Y'-R", or _c(0)-Het-R, a group, or in the presence of two adjacent _CR9 groups, the two phase __Cr9 groups and The bonded carbon atom optionally forms a C6-Ci aryl group which is unsubstituted or substituted by one or more substituents selected from a halogen atom, a straight or branched chain Ci_c6 alkyl group, a hydroxyl group or a CrC4 alkoxy group. 449 201130835 R8 together with the gas atoms bonded by R5 and R5 form the 5 to 9 membered heterocyclyl ring' or R8 is an argon atom; linear or branched chain CrC6 alkyl; CrC4 dentate alkyl; CrC4 hydroxyalkane a CrC10 cycloalkyl group; a 5 to 1 member heterocyclic group; a 4 to 1 membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms, said ring having one, two or three pendant oxy groups Substituted; C6-C1() aryl; 5 to 10 membered heteroaryl; -L-Het-R,,; -LA; -A-S02-R,; -A-SO-R,,,; AA' ; -ALC(0)NR'R&quot;;-AL-CN;-AC(0)-Hetf-L-CN;-AC(0)-NR'R;-AC(0)z-A',;-AC(0)-R,,,;_A_C〇2_R,;-AC(0)zL-A'&quot;;-AC(0)z~L-CN;-AC(0)-A'-A&quot;;-AC(0)-LR,;-AC(0)-L-CN;-A-Het-L-CN; -AC(0)-L-Het -A' ; -AC(0)-L-Het-LA' ; -AC(0)-L-Het-L-R&quot;' ; AC(0)-L-Het-C(0)-A,; Or an -AC(0)zL-Het-R' group, wherein z is 1 or 2, R' and r, the same or different and each represents a hydrogen atom, a CrC4 dentate group, a CrQ thiol group, or a linear chain Or a branched chain CrC6 alkyl group which is unsubstituted or substituted with a cvc2 alkoxy group or a 5 or 6 membered heterocyclic group, and R"' represents a straight or branched chain c]-c0 alkyl group, CrC4 alkane The heterocyclic group and the heteroaryl group are optionally fused to a phenyl group, and wherein the cycloalkyl group, heterocyclic group, aryl group and heteroaryl group are unsubstituted or one or more a dentate atom, a hydroxyl group, a fluorenyl group, a CrC4 alkoxy group, or a linear or branched chain CrC4 alkyl group, the alkyl group being unsubstituted or substituted by a cyano group, and wherein L is a linear or branched chain Cl_c6 An alkyl group which is unsubstituted or substituted with one or two hydroxyl groups, Het Table 0 or NR, and Het, represents NR' where R is a hydrogen atom, 450 201130835 direct bond or knife branch Cl-C4 yard base, c "c4 tooth burnt base or crC4 burned base, γ' represents · (: (〇 )_, so or s〇2, AA, A" and A'', the same or different and each represents C3_C10 naphthenic: 5m to ^membered heterocyclic group; 4 to 1 containing 1, 2 or 3 nitrogen atoms 〇, the ring is substituted by one, two or three pendant oxy groups; a '5 to 10 membered heteroaryl group or a monocyclic C5_C6 aryl group or a heterocyclic bond to a 5 to 6 membered cycloalkyl or heterocyclic ring a bicyclic group, the two '=, a heterocyclic group, a silk, a heteroaryl silk, and a bicyclofilament substituted or via a sulfonate, a thiol, a linear or a branched CVC4 Hexyl, crc: 4 hydroxyalkyl or c丨-c4 alkoxy. The compound of any one of the claims, wherein the group is 5' and + R5 is as defined in claim 1 or 2. The compound of any one of the claims, wherein the non-wind atom, the _ atom, the thiol group, the cyano group, the linear or branched chain, the 16 alkyl group, the crc4 _ alkyl group, the Ci_c4 Hydroxyalkyl, C "C4 alkoxy, 4 alkoxy group, (VC7 cycloalkyl, phenyl, pyridyl, 6-membered saturated-NR'-C(〇)〇Ri3 A® &gt; -C(〇 HCH2)n-R13 Affl 'π 14 group or _C(0)_(CH2)n_NRi3Ri4 group, wherein n, Ri3 and Rl4 are as defined in item 1 of the patent application; and R1 is better in Bayi a hydrogen atom, a halogen atom, a cyano group, a linear or =, a chain CVQ group, or a cyclopentyl or _NRi3Ri4 group, wherein π and RM independently represent a hydrogen atom, or a straight or branched chain port - a gas storm, and 451 201130835 wherein 1 more preferably represents a hydrogen atom or a -NR13R14 group, wherein R13 and R!4 independently represent a hydrogen atom, or a straight or branched chain Crc3 alkyl group; and wherein Ri best represents a hydrogen atom 6. A compound for use in any of the scope of the patent application, wherein R2 represents a hydrogen atom, a halogen atom, a trans group, a cyano group, a linear or branched chain Cl-C6 alkyl group, Crc 4-alkyl, crC4 alkoxy, CVC4 hydroxyalkyl, CrC4 alkoxycarbonyl, C; 3-C7 cycloalkyl, phenyl, pyridyl or 6-membered saturated N-containing heterocyclyl ring; and wherein R 2 is preferred And a hydrogen atom, a halogen atom, a cyano group, a linear or branched chain group, or a C3-C7 cycloalkyl group; and wherein R2 more preferably represents a hydrogen atom or a halogen atom; and wherein R2 preferably represents a hydrogen atom. 7. A compound for use according to any one of the claims, wherein R3 represents a hydrogen atom, a halogen atom, a cyano group, a linear or branched chain CrC6 alkyl 'CrC4 tooth alkyl 'CrC4 hydroxyalkane a CVQ alkoxy group, a CpC4 grafted oxygen group, a C:3-C7 cycloalkyl group, a phenyl group, a 5- to 6-membered heteroaryl group containing at least one hetero atom selected from fluorene, S and N, or a 6-membered saturated n Heterocyclyl ice The dentate, hydroxyalkyl, alkoxycarbonyl, cycloalkyl, phenyl, heteroaryl and heterocyclic groups are unsubstituted or one or more selected from the group consisting of dentate atoms, hydroxyl groups, Substituted with a cyano group, or a substituent of a straight or branched chain CrC0 alkyl group, and the alkyl group is unsubstituted or substituted with one or more cyano groups; or R3 represents -s(0)2nr13r14 a group, a -nr13s(0)2nr14 group, an -OR13 group, a -C(0)0R13 group, a -NR13R14 group, 452 201130835 -NC(0)-(CH2)n-R13 group, _c( 〇)_(CH2)n_NRi3Ri4 group, -NRnCCOHCH2)^4 group or -NRi3C(〇)(CH2)n NRi4Ri5 base, 'where! G or 1 H3, Ru and R15 each independently represent an argon atom, a cyano group, a linear or branched chain CrC6 alkyl group, a CrC4 tooth alkyl group, a CrC4 alkyl group, a Cl-C4 alkoxy group, a C3-C7 ring. An alkyl group, a phenyl group or a 6-membered saturated N-containing heterocyclic ring. 8. The compound for use as described in claim 7 wherein R3 represents a hydrogen atom, a halogen atom, a cyano group, a Ci_C4 haloalkyl group, a CH^cycloalkyl group, a phenyl group, and contains 1, 2 or 3 a 5 to 6 membered monocyclic heteroaryl group selected from the group consisting of ruthenium, osmium and a hetero atom of S, the phenyl group and the heteroaryl group being unsubstituted or one or more selected from a halogen atom, a hydroxyl group, a cyano group, or a straight The chain or branched chain is substituted with a CrC6&amp;base; or R3 represents a -C(〇)〇Ri3 group or a -C(0)-(CH2)n-NR13R14 group, wherein Rn and Rh independently represent a hydrogen atom a cyano group, a linear or branched chain CrC6 alkyl group, a CrC4 dentate alkyl group, a Crc4 hydroxyalkyl group, a Ci_c4 alkoxycarbonyl group, a CrC:7 cycloalkyl group, a phenyl group or a fluorene-containing heterocyclic ring; Wherein R 3 preferably represents a halogen atom, a halogen atom or a cyano group or a -CXOHCiyn-NR group 3!^4 group wherein η is 〇 or 1 and r 3 and R 14 each independently represent a hydrogen atom, or a straight chain or a branch Chain CrC3 alkyl; and wherein &amp; preferably represents a halogen atom or a cyano group. 9. The compound for use according to any one of the preceding claims, wherein R4 represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a linear or branched chain crc6 alkyl group, a crc4-alkyl group, a CrC4 hydroxyalkyl group. (^(^) 453 201130835 oxy, crC4 alkoxycarbonyl, c; rC7 cycloalkyl, phenyl, acridinyl or 6-membered saturated N-containing heterocyclyl ring; and wherein &amp; preferably represents a hydrogen atom, a functional atom, an aryl group, a straight or branched chain CrQ alkyl group, or a cycloalkyl group; and wherein R4 more preferably represents a hydrogen atom. 10. A compound for use according to any one of the preceding claims 'wherein Rs represents a hydrogen atom, or a linear or branched chain CrC6 alkyl group, and the alkyl group is selected from the group consisting of a thiol group, a cyano group, a linear or branched chain 5rC6 alkyl group, a CrC4 (tetra) group, and a CrQ group. a substituent of a c3_c7 cycloalkyl group, a phenyl group or a 6-membered saturated N-containing heterocyclyl ring; and wherein R5 preferably represents a hydrogen atom, a straight or branched chain Ci_C6 alkyl group, said alkyl group being CrC7 cycloalkyl substituted; and wherein the rule 5 is more preferably a hydrogen atom, or a linear or branched C]-C3 alkyl group. The compound for use according to item j of the patent scope, wherein mΑ represents a hydrogen atom, a straight-chain or branched CVC6 alkyl group substituted by a silk or substituted by an oxa-c2 decyloxy group; and ', R6 and R7 are compared Each independently represents a money, or a linear or branched cvc3 alkyl group. The use of any of the above-mentioned targets and the R7 independently represent a hydrogen atom, or a straight chain or a branched chain. And a compound or a straight chain or a compound for use thereof, wherein R0 and preferably each of the branched chain CrC3 alkyl groups. 13. Patent Application No. 1 454 201130835 where ^ represents a linear or branched chain) _(CrC4 silk base), = p 6 recorded, heart. 4 · silk, - (Ci-C6 2 or 3 selected from N 〇; ~ ring wire, benzene a group, a naphthyl group, containing a ?, a group containing 1, 2 or 3 heterocyclic groups selected from 5 to 6 members of a monocyclic heteroaryl group, containing 5 to 7 or containing a hetero atom of Bu 2 , 〇 and S Monocyclic/a nitrogen atom of a CrC7 heterocycloalkyl ketone group, a 5- or t-heteroaryl group of a heterocyclic group or a heterocyclic group directly bonded to a 5- to 9-membered naphthenic group selected from 0, s and said heterofilament or miscellaneous The ring group contains at least one hetero atom of 5 and fluorene, and the lion is singular, stupid, naphthyl, heteroaryl, heterocyclic, heterocyclic, and unsubstituted or selected. From the "atom atom; the base; the aryl group; the linear or branched bond = rC4 S wire; C3_C7 loop wire; secret, the secret has not taken $ or a plurality of substituents selected from a 4-cell atom or a cyano group Substituted; 5 to 6 membered monocyclic heteroaryl group containing 2 or 3 hetero atoms selected from N, fluorene and s, said heteroaryl group being unsubstituted or one or more selected from a halogen atom or a cyano group Substituent substitution; 6-membered saturated N-containing heterocyclyl ring; _s(0)2R1 fluorene group; - fluorene (9) 仏 & & & 基 基 & - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - C(O)〇R10 group; _c(〇)_ch2-OR1() group; -C(O)-(CH2)nO-(CH2)pR10 group; -C(O)-(CH2)nO- (CH2) p-〇-R10 group; _(:(〇Η(:Η2)η·Ι110 group; -NRhjRu group; -C(0)-(CH2)n-NRn)Rii group; R^CCOHCHzX-NRnR^ group; -C(CrC4 alkyl group h-QOMO^VNRnjRn group; -(CrC4 alkyl)-CN group or -(CrC4 alkyl)-C(0)NR'Rn group , where R' and R" are the same or different 455 201130835 ===:=—where each... R10, R , ,, Ώ Each p is an integer from 1 to 3, and its towel or knife branch is CrC6 alkyl; c 11 atom, cyano, linear cycloalkyl Stupid.r 1 4 _alkyl; Cl-C6 hydroxyalkyl; C3-c7 has 2, 3 or 4 4) _ (stupid); -c (〇h stupid); Cycloheteroaryl; 5 to 6 membered 5- to 6-membered monocyclic heteroaryl containing a hetero atom of /, 2, and S. A*3 nitrogen atoms and 1 or 2 heteroatoms of _ To 6 / 2 or 3 selected from N, 〇 and S aryl direct bonds _ 5 = ff base; or monocyclic aryl or hetero, de 3 or 2 selected from Ν, 〇 and The sulfonium, phenyl, heteroaryl, heteroaryl ketone, heterocyclic group, and de-peak or substituted- or a plurality of substituents selected from the group consisting of: 4, ^, , hydroxy, cyano; straight or branched chain Cr (:6 alkyl; Ci_c4 halogen ternary earth, CrC4 hydroxyalkyl, · crC4 alkoxy; unsubstituted or substituted by one or more atoms a 5 to 6 ^ monocyclic heteroaryl group containing 2 or 3 nitrogen atoms, which is unsubstituted or has one or more linear or branched CrC3 alkane Substituted; or a c3_C7 heterocycloalkyl ketone group containing 2 or 3 nitrogen atoms, the heterocycloalkyl ketone group being unsubstituted or substituted by one or more Crc3 alkyl groups; or a heart representing -S(0) 2NR] a 3R14 group, a _NR13S(0)2NR14 group, a -0Ri3 group, a -C(0)0R13 group or a -C(0)-(CH2)n-NR13R14 group, wherein each η is 〇 or 1 And each of R13 and r14 independently represents a hydrogen atom; 456 201130835 a cyano 'linear or branched chain cvq·, the alkyl group is not substituted with a plurality of phenyl groups; cvy silk; a CrC4 ship-based aerobic group; a C3-C7 group; a stupid or 6 s saturated N-containing heterocyclyl ring, or R8 together with a nitrogen atom bonded to R5 and R5, forming a 5 to 9 membered saturated heterocyclic group containing - or -nitrogen An atom as a heteroatom and which is a 5 to 6 membered monocyclic ring containing i, 2 or 3 heteroatoms selected from N, 0 and s, ':l〇i(ci)n'Ri0 group or -c(〇 HCH2)n^A, each of 11 is 0 or Bu and each of R10 and Rn independently represents c C = group, linear or branched chain Cl_C6 alkyl group, anti-burning group, Changan 1 person, and CrQ alkoxy a C3_C7 cycloalkyl group, a phenyl group or a 6-membered saturated N-containing heterocyclic ring, provided that m is 〇 R8 is not _s (square group, tear uS⑼ concept 〇~ · 14 group or groups. For example, the compound used in the scope of the patent scope 帛13, the ring produced 8^ or branched chain CrC6 filament, C "C4 halogen filament, C3-C1 () base 'naphthyl" contains or 3 selected from N And s Ο 5, Q, 5 to 6 membered monocyclic heteroaryl, containing 11, 2 or 3 selected from N, aryl or hetero=== 7 membered heterocyclic group or containing (4) group, The λίίίί to the heterocyclic ring of the heterocyclic ring of the 9-membered heterocyclic ring=heterocyclyl or heterocyclic group containing at least one selected from the group consisting of Ov'S and alkyl, chiral alkyl, alkoxy, cycloalkyl , phenyl, naphthyl, 'methane-based, and bicyclic, unsubstituted or substituted by one or more selected from 457 201130835: ray, thiol, cyano, straight or branched c "c6 alkyl" crc4 tooth., c3_c7 cycloalkyl, unsubstituted or substituted by - or a plurality of im atoms, containing 2 or 3 heteroatoms selected from N, o and S 5 to 6 M monocyclic heteroaryl, 6-membered saturated ring, Nacheng sulfonyl group, _S(O)2NRl0Rn group hetero-NR10s(o)2NRll base ' _〇Ri〇 圏-C (9)- (CH^o group, _NRi〇Rn group; group, -C(〇HCH2)n-NR1〇Rll ^®.ic-R 10C(〇HCH2)n-NRllRl2 &amp; group '-(Q-C4 alkyl)_CN group or _(Ci_c4 alkyl)_c(9) 聊团' where R' and R" are the same or different and are selected from hydrogen atoms and straight a bond or a branched chain CrC4 alkyl group; wherein 11 is ruthenium or 1, and the knives Rio and Rn each independently represent a hydrogen atom, a cyano group, a linear or branched chain crc6 alkyl group 'CrC4 dentate base, C3 &lt;:7 cycloalkyl, phenyl, 2 or 3 5- to 6-membered monocyclic heteroaryl selected from heteroatoms of N, fluorene and s, 5 to 6 membered heterocyclic ring containing hydrazine, 2 or 3 nitrogen atoms a double-filament or a hetero-containing group having a mono- or heteroaryl group directly bonded to a 5- to 6-membered cycloalkyl or heterocyclic group containing a fluorene, 2 or 3 nitrogen atoms, An alkyl group, a cycloalkyl group, a phenyl group, a heteroaryl group, a heterocyclic group, and a bicyclic group are unsubstituted or substituted by one or more (d) substituents from: a self atom; a thiol group; a direct bond or a branching bond Ci_c6; a C4 halogen-based group; a 5- to 6-membered monocyclic heteroaryl group which is unsubstituted or substituted with one or more self-substituted atoms, and has a 5- to 6-membered monocyclic heteroaryl group. Unrecorded money - or township thieves continue to burn the base to take the plant or 3 have 12 or 3 nitrogen atoms (: 3_〇7 heterocycloalkyl ketone group, 458 201130835 said heterocycloalkyl ketone group Substituted or substituted with one or more crc3 alkyl; or r8 represents a -s(o)2nr13r14 group, -NR13S(0)2NR14 group, -OR13 group, -C(0)0R13 group or -C (〇HCH2)n-NR13R14 group, wherein each η is 0 or 1, and R13 and R14 are independent a straight or branched chain CrC6 alkyl group, a CrC4 alkyl group, a CrC4 hydroxyalkyl group, a CrC4 alkoxycarbonyl group, a C3-C7 cycloalkyl group, which represents a hydrogen atom, a cyano group, or is unsubstituted or substituted by one or more phenyl groups. a phenyl or 6-membered saturated N-containing heterocyclyl ring; or R8 together with the nitrogen atom to which R5 and R5 are bonded form a 5 to 9 membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and Substituted by a -C(O)-(CH2)n-R10 group or -(^(OXCHyn-NRioR^ group, wherein η is 0 or 1' and ri() and independently represents a hydrogen atom, a cyano group, a straight Bond or branching bond CrC6 炫, C1-C4 dentate, C1-C4 alkyl, C1-C4 alkoxy, c3_c7 cycloalkyl, stupid or 6-membered saturated N-containing heterocyclic ring, the limitation The condition is that when rn is 0, R8 is not -S(〇)2NR13R14* group, -nr13s(o)2NRi4 group or -〇R13 group. 15. If the patent application is in the 13th or 14th item Said a compound for use, wherein R8 represents a linear or branched chain CrC6 alkyl group, CrC4 halogenated group 'Cr &lt;:4 alkoxy group, CrC7 cycloalkyl group, adamantyl group, phenyl group, 5- to 6-membered monocyclic heteroaryl group containing 2 or 3 hetero atoms selected from N, fluorene and S 2 or 3 5- to 7-membered heterocyclic groups selected from heteroatoms of N, hydrazine and S, or containing a phenyl group directly bonded to 5 to 7 members containing at least one hetero atom selected from the group consisting of hydrazine, S and N a bicyclic group of a ring group, 459 201130835 wherein the alkyl, haloalkyl, alkoxy, cycloalkyl, adamantyl, strepto, heteroaryl, heterocyclyl and bicyclic groups are unsubstituted or have one or more One selected from a halogen atom, a hydroxyl group, a linear or branched Crc6 alkyl group, a phenyl group, a pyridyl group, -s(o)2r1g, -C(0)0R1(). , -NRi〇r&quot; group, -CCOMCfyn-NR^R&quot; group, _(Crc4 alkyl)_CN group or -(CrC4 alkyl)-C(0)NR'R'· group substituent Substituted, r and R" in the pot are the same or different and are selected from the group consisting of a gas atom and a linear H-bond group, wherein η is 0 or 1, and 10 and Ru each independently represent a hydrogen atom, a cyano group, a straight chain or a chain. CrC6 alkyl, CrC4 dentate, c3_c7 cycloalkyl, phenyl, containing 2 or 3 heteroatoms selected from N, 〇 and s, 5 to 6 membered monocyclic C C containing ^, Λ or 3 a 5- to 6-membered heterocyclic group of a nitrogen atom, or a heteroaryl group directly bonded to a 5- to 6-membered cycloalkyl group or a hetero group: a starting group or a hetero group containing 2 or 3 nitrogen atoms 3 , alkanoyl, cycloalkyl, phenyl: hydrazine and = unsubstituted or substituted by one or more CrC4 dentate groups selected from the group consisting of: chaotic, straight or branched chain Ci_C6 alkyl a, · it Λ or Substituted by a ❹-α atom, '' aromatic: 5 to 6 members of a single ring heteroaryl group having 3 atoms of the undesired f, the singular atom of the heterocyclic ketone group Generation or passage—or multiple straight or branched gold hearts representing the collar 13 group, where the Rl3 table An unsubstituted or hexaminated 460 201130835 multiple phenyl substituted 匸 匸 3 烧, or R 8 together with the bonded nitrogen atom to form a 5 to a saturated heterocyclic group containing - or two nitrogen An atom as a hetero atom and a pot of -CCOHCH^o A®3t-C(〇HCH2)n-NR10R11 , /where η is 0 or 1' and RlQ and % independently represent a hydrogen atom, a nitrogen group, a straight chain or a branched chain The CrC is subjected to a radical or a CrC4 sulfhydryl group, and the restriction condition is that when m is oxime, &amp; is not an even 3 group. 16. For the application of the general formula for the money supply of the compound: R9 represents a hydrogen atom ' _ atom, minus, cyano, linear or branched ς cvc6 alkyl, Cl, c4 _ group, CrC4 alkoxy , q々cycloalkyl, -Crc4 alkyl-C3-C7 cycloalkyl, phenyl, 5- to 6-membered monocyclic heteroaryl containing 2, 3 or 4 heteroatoms selected from N, fluorene and S a 5- to 7-membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, S and N, wherein the cyclofilament, phenyl group, heteroaryl filamentous county is unsubstituted or - or more selected from halogen Atom, secret, cyano, straight or branched bond crc6 alkyl, _s(0)2Ri 〇 group, _c(〇)〇R^ group '-C(O)-(CH2)-R10 group or _ Substituted by a substituent of the 〇Ri0 group, wherein Rio represents a hydrogen atom, a cyano group, a linear or branched bond c group, a Crc4_alkyl group or a c3_c7 cycloalkyl group, wherein 470 wherein the cycloalkyl group is unsubstituted or via one or a plurality of substituents selected from the group consisting of a dentate atom, a hydroxyl group, a cyano group, a linear or branched chain Cl_C:6 alkyl group, or a Ci_c4 alkyl group; or R9 represents a -S(〇)2R13 group, -〇r13 a group, _c(〇)〇R, 3 group, -NR13R14 group or -C(0)_(CH2)n_NR An i3Ri4 group, wherein n is 〇 or 461 201130835 1 and Rl3 and rI4 are each independently a fluorene group (C: C4 alkyl group WC, .C4 methoxy group) or ??, s, and N heteroatoms 5 to 7 membered heterocyclic group) i. In the case of two _CR9 adjacent groups, two adjacent CR groups and their bonded carbon atoms contain at least one of the heteroaryl groups. Substituents selected from the group consisting of hydrazine, S, and aryl, and heteroaryl are unsubstituted or substituted with one or more: ', ', S ▲ straight or branched chain crC4 alkyl. The compound for use as described in claim 16 of the patent scope, wherein t 9 = "sub" „ atom’ via a radical or a branched chain '6 ^ 1 &lt;: 4 tooth-burning base 'CrC4 alkoxy group, CrC7 cycloalkyl group, 1, 4, tertino C3-C7 alkyl group, phenyl group, containing 2 or 3 hetero atoms selected from n, s a 6-membered monocyclic heteroaryl group, a 5- to 7-membered heterocyclic group containing at least one hetero atom of a group, and a hetero atom of N, the alkyl group, a pyridyl group, an alkoxy group, a cycloalkyl group, a phenyl group a heteroaryl 2 hetero 3 group unsubstituted or via- or a plurality selected from a halogen atom, a hydroxyl group, a ^ a ^ or a branch bond Cl &lt;:6 alkyl, -C(〇)-(CH2)_R10 group or a substituent of the -ORio group, wherein Rio represents a hydrogen atom, a nitrogen group, a direct bond or a branched bond Ci_c group, and a CrC4 fluorenyl group Or a cycloalkyl group, a f-alkyl group, a fluorenyl group, and a cycloalkyl group which are unsubstituted or one or more, a sub, a thiol group, a cyano group, a linear or branched CVQ group, or a 14 dentate group. a substituent substituted; or R9 represents a 21113 group, a -C(0)0R13 group, a -NR13R14 group 462 201130835 group or a -C(〇HCH2)n-NR13RM group, wherein η is 0 or 1 and Ru And Rl4 independently represents a hydrogen atom, or a linear or branched chain CrC0 alkyl group; or in the presence of two _CR9 adjacent groups, two adjacent _Cr9 groups and their bonded carbon atoms are regarded The case of forming a 5 to 9 membered aryl or heteroaryl group. The heteroaryl group contains at least one heteroatom selected from the group consisting of hydrazine, S and n, which are unsubstituted or one or more Substituted with a halogen-containing fluorene or a linear or branched Crc4 alkyl group. 18. The use of the compound as described in claim 16 or claim 17 wherein the hydrogen atom, the halogen atom 'cyano group, a straight chain or a branched minus a crc4 alkyl group' Crc4 ^ alkyl group, a C3_C7 ring Alkyl, Ci_C3 alkyl A-C7 cycloalkyl-containing 5 to 6 membered monocyclic heteroaryl groups of 2 or 3 nitrogen atoms, having 5 to 7 membered heterocyclic groups of 1, 2 or 3 nitrogen atoms, The alkyl group, cycloalkyl group, heteroaryl group and heterocyclic group are unsubstituted or substituted by one or more substituents selected from a cyano group or a -R10 group, wherein R1〇 represents a hydrogen atom, or a true chain Or a branched chain CrC3 alkyl group, or R9 represents a -S(〇)2Ri3 group, a -C(0)0R13 group, a -NR13R14* ring--C(〇HCH2)n-NR13R14 group, wherein η is 0 or 1 and r13 and Rh independently represent a hydrogen atom or a linear or branched chain CrC6 alkyl group. 19. The compound for use as described in claim 1, wherein m is 0 or }; Z is NR5, x is a nitrogen atom and y is a group -cr9, or y is a nitrogen atom and X is a base ring -CR9 ; 463 201130835 R, represents a hydrogen atom, a dentate atom, a cyano group, a linear or branched bond [c silk, or a C3_c4 ring-form or a -nr13n14 group, wherein R 1 6 each independently represents a hydroquinone. 3 and R丨4 / atom or linear or branched chain appearance; 2 not wind atom, dentate atom, cyano group, leuco, or C3C4@ base; 〃 again bond CVQ to ^ single, cyano, % A cycloalkyl group, 5 Ϊ NO = T group, the heteroaryl group containing 1, 2 or 3 selected or via a plurality of selectors, the aryl group and the heteroaryl group being unsubstituted U. Substituting (tetra) atom, substituting for a chain of a CrC6 filament, or a chain or a NR RC3 (〇tR for its CL〇) 〇Rl3 group, a group or group, wherein R 3 and Independently represents a hydrogen primord, a QC oxo county, a c3_c_ heterocyclyl ring; a 3... a thiol group, a benzyl group or a 6-membered saturated group; ^ a straight or branched chain crc6 R4 represents a hydrogen atom, a halogen atom, a cyano group a group, or a C3-C4 cycloalkyl group; Rs represents a hydrogen atom, a straight or branched chain Ci_C3 alkylalkyl-(:3-(:7-cycloalkyl; r&amp; each independently represents a hydrogen atom, or a straight or branched bond Ci_c3 alkyl group substituted or substituted with Q-C2 alkoxy; R8 represents a straight bond or a branched chain CrC6 alkyl group, Ci_Q(tetra)yl, c cycloalkyl, gold, stupid, containing 1, 2 Or 3 to 6 membered monocyclic heteroaryl groups selected from heteroatoms of N, hydrazine and S, containing 2 or 464 201130835 5 to 7 membered heterocyclic groups selected from heteroatoms of N, hydrazine and S 1, 2 or 3 nitrogen atoms of CH: 7 heterocycloalkyl ketone group, containing a biphenyl group in which a phenyl group is directly bonded to a 5- to 7-membered heterocyclic group containing at least one hetero atom selected from 0, S and N Or contain 吼a group directly bonded to a bicyclic group of a Crc7 cycloalkyl group, wherein the cycloalkyl group, adamantyl group, phenyl group, heteroaryl group, heterocyclic group, heterodazine group, and bicyclic group are unsubstituted or Substituted with one or more substituents selected from the group consisting of: a halogen atom; a hydroxyl group; a linear or branched chain-terminated alkyl group; a styl group which is unsubstituted or one or more selected from a halogen atom or a cyanogen Substituent substituent; 5 to 6 fluorene monocyclic base containing 1, 2 or 3 heteroatoms selected from N, hydrazine and s, said heteroaryl group being unsubstituted or via one or more selected (tetra) Substituted by a substituent of an atom or a cyano group; _s(〇)2Ri〇 group, -C(O)OR10; -C(〇)-CH2-〇R10 group; -C(O)-(CH2)nO-( CH2) pR10 group; -C(〇HCH2)n-〇-(CH2)p-〇-R10 group; _c(〇)_(CH2)n_R(7); _NR10RU group; -C(〇)_(CH2) n_NRi〇Rii group; _c(Ci_c4 alkyl group; _(Crc4 filament)_CN group or -(CrC4 alkyl group, wherein R, and R" are the same or different and are selected from argon atoms and linear or branched Key cc alkyl; or an integer of (1), and wherein ... to an integer of 3, and 7; is 0 R1 And Ru each independently represent a hydrogen atom, a cyano group, a straight or a branched chain CrQ alkyl 'Cl-C4 dentate alkyl group' CrC6 hydroxyalkyl group, a C3_C7 cycloalkyl group, a phenyl group, a -(CrC4 hydroxyalkyl group)- (phenyl), _c(〇)_(phenyl), 5- to 6-membered monocyclic heteroaryl 465 containing 1, 2 or 4 heteroatoms selected from N, (10) and S 201130835 base 'containing 1, 2 Or 9 of 3 nitrogen atoms to have 2 or 3 gas atoms and! Or 2 aryl, containing aryl fluorenyl, containing 1, 2 or 3 selected from 5 to 6 membered heterocyclic rings of N to 6 members, or 5 to 6 containing single ring &amp; The bicyclic radical direct bonding group of the cycloalkyl or heterocyclic group contains 1, 2 or 3 hetero- or tetra-containing groups selected from N, fluorene and s, the cycloalkyl group, the phenyl group, and the heteroaryl group. a group, a heterocyclic group and a substituent, substituted with - or a plurality of substituents selected from the group consisting of: unsubstituted; cyano; straight or branched chain CrQ alkyl; Ci_c4 dentate, hydroxy group; Crc4 a phenyl group, which is substituted with a poly-? atom atom; contains 2 or 3 nitrogen atoms to: eat a ring heteroaryl 'the filament is unsubstituted or via- or a plurality of linear chains: , crc3 Substituted by a silk; or a c^cyclodextrin group containing 2 or 3 nitrogen atoms, which is unsubstituted or substituted with one or more straight or branched chain crc3 alkyl groups; or Rs Is a -ORu group, wherein Ri3 represents unsubstituted or crc3 alkyl substituted with ~ phenyl, or a R8 together with Rs and a nitrogen atom bonded to R5 form a 5 to 7 member saturated heterocyclic group' It contains one or two nitrogen atoms As a hetero atom and substituted by a thiol group, a -C(O)-(CH2)n-R10 group or a -QohcHA-NRhjR&quot; group V*, wherein each η is 〇 or 1, and wherein each r1〇 Independently represents a hydrogen atom, a cyano group, a linear or branched chain, or a Cr (:4 haloalkyl ' ^ R9 represents a hydrogen atom 'halogen atom, a cyano group, a straight or branched chain 466 201130835 alkyl a crc4 dentate alkyl group, a c3-c7 cycloalkyl group, 5 to 6 members containing a hetero atom selected from N, fluorene and S, 2 or 4 or 2 or 2 hetero atoms selected from the group consisting of Ν, 0 and S a 5- to alkyl group, wherein the alkyl group, the group, the heteroaryl group, and the heterocyclic group are not = or via - or a plurality selected from a halogen atom, a cyano group, a hydroxyl group, a linear CrC6 alkyl group, -S ( O) 2R10 group, _C(〇)〇R] thiol-C(〇HCH2)_R10 group or a substituent of the -OR10 group, wherein r represents a hydrogen atom, a cyano group, or a straight or branched chain CrC3^//10 r9 represents a -s(o)2r13 group, a -or13 group, a _c(〇)〇Ri3 group, a -NR13R14 group or a -C(〇HCH2)n-NR13R14 group, wherein n Is 〇 or 1 and R!3 and Ru each independently represent a hydrogen atom, a straight chain or a branched chain , -(crC4 alkyl)-(crC4 silk) or _(CrC4 alkyl)_ (5 to 7 membered heterocyclic groups containing up to 6 to a hetero atom selected from the group consisting of hydrazine, S and N); In the case where two -CR9 adjacent groups are present, the two _CR9 groups and the carbon atoms to which they are bonded form, as the case may be, 5 to 6 membered aryl groups, unsubstituted or via- or multiple selected from The substituent of the prime atom, ί straight chain Ci-Q alkyl group is substituted, and the restriction condition is that when m is 〇, r8 is not a -OR13 group. 20. For the use of A, as described in item i or item 2 of the scope of application. m is 〇 or 1; z is nr5; group is a nitrogen atom and γ is a group, or γ is a nitrogen atom and x is 467 201130835 Rl represents a hydrogen atom, a halogen atom, a cyano group, a linear or branched chain crc6 Alkyl, or OK: 4 cycloalkyl 4_NRl3N 4 group, wherein Ri3 and ~ each independently represent a hydrogen atom, or a linear or branched chain CrC3 alkyl; R2 represents a hydrogen atom, a halogen atom, a cyano group, a straight a chain or branched chain Ci_C6 alkyl group, or a CVC4 cycloalkyl group; R: a gas atom, a halogen atom, a cyano group, a CrC4 cycloalkyl group, a 5- to 6-membered monocyclic aryl group or a heteroaryl group, said heteroaryl group Containing 1&gt; 2 or 3 heteroatoms selected from N, 0 and s 'the aryl group and the heterofilament unsubstituted or one or more selected from the group consisting of _ atoms, minus, cyano, or straight or branched chains Substituted with a substituent of a CrC6 alkyl group, or R3 represents a Nape 3 group, a _c(〇)-NRi3Ri4 group or a moma group, wherein shame and shame each independently represent a nitrogen atom or a branched crc6 group. , CrC4 tooth base, crc4 burnt base, CVQ silk county, C3_C7 cyclofilament, phenyl or heterocyclic ring; R4 represents hydrogen atom, _ atom, cyano group, direct bond leukoxene, Cvc4 ring filament; Cl Q alkyl group == base, __to silk, or w R7 each independently represents a hydrogen atom, or a straight or branched chain V R8 represents a linear or branched chain CrC6 alkyl group, CrC4 _ alkane Oxygen, C; rC7 ring yard base, diamond just base, stupid base, contain! Soil, 2^4 5- to 6-membered monocyclic heteroaryl selected from heteroatoms of N, hydrazine, and s: containing 468 201130835 having 2 or 3 heteroatoms selected from N, hydrazine, and s 5 to 7 a heterocyclic group, or a bicyclic group containing a phenyl group directly bonded to a 5- to 7-membered heterocyclic group containing at least one hetero atom selected from the group consisting of hydrazine, s, and N, the alkyl group, the halogen group, the alkoxy group And a cycloalkyl group, an adamantyl group, a phenyl group, a heteroaryl group, a heterocyclic group and a bicyclic group are unsubstituted or substituted by one or more substituents selected from the group consisting of: a halogen atom, a hydroxyl group, a straight chain or a branched chain Ci_c6 Alkyl, stupid, &gt; -S(O)2R10 ^ -C(0)〇R1〇. -C(O)-(CH2)n-R10 &gt; -NR10Rn group, -CCOMCHA-NR^R&quot; a group, a _(CrC4 alkyl))-CN group or a -(CrQ alkyl)-C(〇)NR'R" group, wherein R, and R, are the same or not, and are selected from a hydrogen atom and a straight a chain or a branched chain Ci_c4 alkyl; wherein _ 〇 &gt; and Ru each independently represent a hydrogen atom, a cyano group, a straight bond or a branched alkyl group, a % t-alkyl group, a % cycloalkyl group, a stupid group, and a A 5- to 6-membered monocyclic heteroaryl ring of a hetero atom of S. 5 to 6M heterocyclic groups of 3 nitrogen atoms, or 5 pairs of &amp;= directly bonded to 5 to 6 M cyclofilament or heterocyclic f-filament or to a 2 or a nitrogen atom, and a double ring Silk-substituted heterofilament, heterocyclic radical: an alkyl group derived from a single atom or a plurality of substituents selected from the group consisting of: a straight or branched bond CrC6 alkyl group; a heteroaryl group not taken to a 6-membered monocyclic ring An aryl group, said secondary or singular straight chain or branched chain crc3 alkyl group taken at 469 201130835; or CVC containing a 1, 2 or 3 nitrogen atom: 7 heterocycloalkyl ketone group, said heterocyclic ketone group The group is unsubstituted or substituted by one or more straight or branched bond C1-C3 alkyl groups, or R·8 represents a -ORn group, wherein Rn represents unsubstituted or substituted 2/C3 alkyl via one or more phenyl groups , or R8 together with Rs and the nitrogen atom to which the bond is bonded form a 5 to 7 member saturated heterologous base containing one or two nitrogen atoms as a hetero atom and which is via -C(O)-(CH2)n- The R10 group or the -C(0)_(CH2)n-NR1〇Rll group is taken as wherein η is 0 or 1, and R1() and Ru independently represent a hydrogen atom, a cyano group, a straight bond or a branch bond C1-C3 ray base, or C1-C4 _ burnt base; ruler 9 indicates Atom 'halogen atom, cyano group, straight or branched chain ^-sulfonyl group' CrC4 self-burning group, C3-C7 cycloalkyl group, -crC3 yard-C3-C7 cycloalkyl group containing 1, 2 or 3 a 5- to 6-membered monocyclic heteroaryl group of a nitrogen atom, having 5 to 7 membered heterocyclic groups of 1, 2 or 3 nitrogen atoms, said alkyl group, cycloalkyl group, heteroaryl group and heterocyclic group being unsubstituted Or substituted by one or more substituents selected from a gas group or a group, wherein R1() represents a straight or branched chain CrC3 alkyl group, or I represents a -s(o)2r13 group, -cx〇) or13 group a group or a _NRi3r14 group, wherein Ru and each independently represent a hydrogen atom, or a linear or branched chain CrC4 alkyl group, or in the presence of two -CR_9 adjacent groups, two groups and a bond thereof The carbon atom of the junction optionally forms a 5 to 9 membered aryl group which is unsubstituted or substituted with one or more substituents selected from a functional atom, or a linear or branched chain CrC4 alkyl group, 470 201130835, The restriction is that when the melon is 〇, R8 is not a _〇Ri3 group. The compound for use as described in claim 20 (4), wherein m is 〇 or 1; Z is NR5; X is a nitrogen atom and Y is a group -CR9, or Y is a nitrogen atom and X -CR9; Ri represents hydrogen Atom; R2 represents a hydrogen atom; a group, or R3 represents a hydrogen atom, a δ-atom atom, a cyano group, a crc4 halogen group, a cyclopropyl group, an unsubstituted or a phenyl group substituted with a porphyrin atom, containing a Or 3 to 6 noble monocyclic heteroaryl R3 selected from N and a hetero atom of fluorene, which represents a -C(o)〇Rl3 group, a _c(〇) NRi melon group-NR13C(〇)R14 group, The towels Ri3 and Ri4 independently represent a gas atom or a methyl group; R4 represents a rat atom; R5 represents a hydrogen atom, a methyl group, an ethyl group or a _CrC:3 alkyl group_C3_C4 cycloalkane R6 and R/7 are each independently represented a hydrogen atom or a fluorenyl group; Rs represents a linear or branched chain Cr€6 alkyl group, a CrC4 haloalkyl group, a cvc4 alkoxy group, a Q3-C7 cycloalkyl group, an adamantyl group, a phenyl group, containing hydrazine, 2 or 3 a 5- to 6-membered monocyclic heteroaryl group selected from the group consisting of N, 0, and S heteroatoms, having 5, 7 membered heterocyclic rings 471, 201130835, or 1, 2 or 3 hetero atoms selected from N, fluorene, and s, or Containing phenyl directly bonded to a bicyclic group of at least one 5- to 7-membered heterocyclic group selected from the group consisting of a hetero atom of hydrazine, s N, a thiol group, a dentate group, an alkoxy group, a cycloalkyl group, an adamantyl group, a heteroaryl group, a heterocyclic group The cyclic group and the bicyclic group are unsubstituted or have one or more self-commercial atoms, minus, linear or branched bonds, CrC6^, phenyl, octyl, -s(o)2r10, -c_R10, _c(0)_ (CH2)n Ri〇, NNi, -C(〇HCH2)n-NR丨. Substituent substitution of a Ru group, a cinnamoyl)-CN-(C1-C4 alkyl)-C(〇)NR'R" group, wherein R" is the same or different and is selected from a hydrogen atom and a straight or branched chain; wherein η is 0 or 1, and 4 such that Rio and R „ each independently represent a hydrogen atom, a cyano group, a linear or branched Q-C6 alkyl 'CrC4 g alkyl group, a CrC7 naphthenic ring a phenyl group, a 5- to 6-membered monocyclic heteroaryl group containing j, 2 or 3 hetero atoms selected from N, fluorene and S, containing 5 or 6 membered heterocyclic groups of 2 or 3 nitrogen atoms, or The monocyclic CVQ aryl or heteroaryl group is directly bonded to a bicyclic group of a 5 to 6 membered cycloalkyl or heterocyclic group containing 1, 2 or 3 nitrogen atoms: the alkane a group, an alkyl group, a cycloalkyl group, a phenyl group, a heteroaryl group, a heterocyclic group, and a bicyclic group are unsubstituted or substituted with one or more substituents selected from the group consisting of a dentate atom; a hydroxyl group; a cyano group; Chain or branched chain CrC6 alkyl; Ci-Cj dentate; unsubstituted or substituted by one or more halogen atoms, 5, to a member of a monocyclic heteroaryl group containing 1, 2 or 3 nitrogen atoms The heteroaryl group is unsubstituted or one or more straight Or a branched chain CVC3 alkyl group; or a CrC7 heterocycloalkyl ketone group containing 1, 2 or 3 nitrogen atoms, said heterocycloalkyl group being unsubstituted or via one or more straight or branched chains 472 201130835 crc3 alkyl substituted 'or r8 represents -〇Ri3 group' wherein Rl3 represents unsubstituted or substituted by a plurality of phenyl substituted CrC3 alkyl groups, or Re together with R5 and R5 bonded nitrogen atoms form 5 a 7-membered saturated heterocyclic group containing one or two nitrogen atoms as a hetero atom and substituted with a -C(0)-(CH2)n-Ri〇 group or a -QOHCI^n-NRioRu group wherein η is 0 or 1 ' and Rio and Rii independently represent a hydrogen atom, a straight or branched bond C1-C3 alkyl group, or a Ci_C4 halogen late group; R9 represents a hydrogen atom, a halogen atom 'cyano group, a straight chain or a branched chain c Alkyl, CVCy cycloalkyl' contains 5 to 2 4 monocyclic heteroaryl groups of 1, 2 or 3 nitrogen atoms, 5 to 7 members of the heterocyclic ring containing 1, 2 or 3 nitrogen atoms And the cycloalkyl, heteroaryl and heterocyclic groups are unsubstituted or substituted by a plurality of substituents selected from the group consisting of cyano or -ORio groups, wherein R1〇 represents a straight or branched chain CrC3 alkyl group, or R9 a -S(0)2Ri3 group, a -0(0)01^3 group or a ?νκ13κ14 group 'wherein Rn and R"4 each independently represent a hydrogen atom, or a linear or branched bond CVC4 alkyl group, or In the presence of two -CR9 adjacent groups, the two _cr9 groups and the carbon atoms to which they are bonded optionally form 5 to 6 membered aryl groups which are unsubstituted or have one or more The substituent is selected from a halogen atom or a linear or branched minus CrQ alkyl group, and the restriction is that when it is pseudo-quinone, R8 is not an -OR13 group. And the compound for use as described in claim 1, which has the formula (I"), 473 201130835 Formula (i,,) wherein X is a nitrogen atom and Y is a -CR9 group, or Y is a nitrogen atom and X is a CR9 group; R3 is an argon atom, a halogen atom, a cyano group, a -C(0)0W group , C3-C4 cycloalkyl, acridinyl, oxazolyl or phenyl, said phenyl being unsubstituted or substituted by a halogen atom, wherein R' is an argon atom, or a straight or branched chain Crc4 alkyl; R5 Is a hydrogen atom, a mercapto group, an ethyl group, a -(CH2)-cyclopropyl group; or R5 together with a nitrogen atom bonded to R8 and R5: 1,4-diazepan-1-yl, The 1,4-diazepan-1-yl is unsubstituted or substituted with a -C(0)CH2CN group, or a pyrrolidinyl group which is unsubstituted or pyridyl or -C (0) N(CH2CH3)2 group substituted; R6 and R7 each independently represent a fluorene atom, or a straight or branched chain crc3 alkyl group which is unsubstituted or substituted by a crc2 alkoxy group; R8 together with a bond of R5 and R5 The nitrogen atom of the knot together forms the 1,4-diazepan-1-yl or pyridinyl group; or r8 is a hydrogen atom, a straight chain or 474 201130835 &gt; a branched CVCf group, _(Ci_c5 ^ )_(Ci_C2 alkoxy), cyclohexyl, t-calcinyl, stupid 1 , 5,6,7,8-tetraindole, tetrahydropyranyl or 10-alkyl, the cyclohexyl, adamantyl, phenyl, π-biti, tetrazinyl, tetrahydrone And the alkyl group is unsubstituted or substituted with one or more substituents selected from the group consisting of a halogen atom, a hydroxyl group, a -CH2CN group, a linear or branched chain CrC3 alkyl group, or a CrC4 alkyl group; or Rs is a piperidine Pyridyl, piperazinyl, pyrrolidinyl or pyrrolidin-2-one, said piperidinyl, piperazinyl, pyrrolidinyl and pyrrolidin-2-one are unsubstituted or selected by one or more From straight or branched chain CrC3 alkyl, phenyl, tIpyridyl, triazolyl, thiazolyl, -S(0)2.(CH2)nR1〇 group, _c(〇)_(CH2)n〇 Ri〇 group, -C(O)-(CH2)nR10 group, _c(〇)_(CH2)n_N(Ri〇)_(CH2)nRii group, -(CVQalkyl)-CN group or a _(crc4 alkyl)-C(O)NR10R::^ substituent substituted wherein η is 〇 or 1, and wherein the phenyl, acridinyl, triazolyl, and thiazolyl are unsubstituted or one or Substituting a plurality of substituents selected from a dentin atom, a hydroxyl group, a cyano group, a linear or branched chain Cl-C3 alkyl group, or a CrC4 haloalkyl group, and wherein Rii a hydrogen atom, or a linear or branched chain CrC4 alkyl group, and Rio represents a hydrogen atom; a cyano group; a linear or branched chain CrC5 alkyl group; C "C4 haloalkyl group; CrC5 hydroxyalkyl group; (qQ alkyl group) (CrC2 alkoxy); CrC6 cycloalkyl 'the polar group is unsubstituted or one or more selected from the group consisting of halogen, atom, hydroxyl, cyano, straight or branched chain Ci&gt; C3 alkyl, crc3 halogen Substituted with a substituent of an alkyl group, a -(CrC4 alkyl)-CN group or a phenyl group; a pyridyl group which is unsubstituted or substituted with one or more substituents selected from a dentate atom or a cyano group Substituted; phenyl, which is unsubstituted or substituted with one or more substituents selected from 475 201130835 halogen atom, cyano group, linear or branched chain CrC3 alkyl group, or CrC4 hydroxyalkyl group; The transcription is unsubstituted or substituted with one or more substituents selected from a sulfinyl group or a cyano group; a pyrimidinyl group which is unsubstituted or one or more selected from a halogen atom, a hydroxyl group, Or a substituent of a straight or branched chain CrC3 alkyl group; the thiazolyl group, which is unsubstituted or has one or more selected from a functional atom, a cyano group, Or a substituent of a linear or branched C1-C3 alkyl group; an imidazolyl group, -(CrC5 alkyl fluorenylphenyl), wherein the phenyl group of _(Ci_c5 alkyl)-(phenyl) is unsubstituted or Substituted by one or more substituents selected from a sulfonium atom or a Ci_C2 alkoxy group; _(Cl-C5 hydroxyalkyl)-(phenyl), wherein the -(CrC5 hydroxyalkyl)-(phenyl) The phenyl group is unsubstituted or substituted with one or more substituents selected from a halogen atom or a Crc2 alkoxy group; 1-thia-2,3-diazolyl, said 1-thia-2,3-diazole Substituted unsubstituted or substituted by one or more straight or branched chain CrC3 alkyl; benzomeridyl, said benzimidazolyl unsubstituted or substituted by one or more linear or branched CrC3 alkyl ; alkyl; 2,2-dimercapto-1,3-dioxolane; imazide; 朵 朵 ;; tetrahydro bridging; tetrastone; triwax; Base, benzhydryl or pyrimidine, 2,4(1H,3H)-dione; rule 9 is a hydrogen atom; a halogen atom; a cyano group; a CrC4 haloalkyl group; a linear or branched chain CrC3 alkyl group; a C4 cycloalkyl group; an acridinyl group, the 11-pyridyl group being unsubstituted or one or more selected from a hydroxyl group or a CrC3 alkoxy group Substituted; triazolyl; tetrazolyl, unsubstituted or substituted by one or more straight or branched chain CrC3 alkyl; pyrrolidinyl, unsubstituted or pyrrolidinyl One or more _C(0)0R, 13 group substituted; piperazinyl, said hexyl group unsubstituted or one or more selected from linear hydrazine branches 476 201130835 CrC3 alkyl, or Substituent substitution of _S(0)2R&quot; 13 group; morpholinyl; • S(0)2R13 group; _〇r13 group; _c(〇)〇Ri3 group; _NRi3ri4* group or -C( 0)-(CH2)n-NR13R14 group; or when γ is a group core, two adjacent R9 groups together with the carbon atom to which they are attached may form a benzene ring; wherein η is 0 or 1 and each R1 And Ri4 independently represent a hydrogen atom, a linear or branched chain CrC3 alkyl group, -(CVC3 alkyl)-(CrC2 alkoxy group), -(CrC3 alkyl)-((pyridinyl); or _(Cl_C3) Alkyl)-(morpholinyl); r, i3 represents a hydrogen atom, or a linear or branched chain CrC3 alkyl group; and R, 13 represents a linear or branched chain CrC3 alkyl group. 23. The compound for use as described in claim 1 or 2, which has the formula (Γ), Wherein X is a nitrogen atom and Y is a -CR9 group, or γ is a nitrogen atom and X is a CR9 group; - a R3 is a hydrogen atom, a halogen atom, a cyano group, a -C(0)0R fluorenyl group a group, c3-c4, alkyl, pyridyl, pyrazolyl or phenyl substituted by a phenyl group, wherein R is a hydrogen atom or a straight or branched bond 477 201130835 alkyl ; r5 is a hydrogen atom, a methyl group, an ethyl group, a _ch 2 · cyclopropyl group, or R 5 together with a nitrogen atom bonded to R 8 and R · 5 together form a 1,4- 氡 择 择 、, p 1 group '赖·丨仙尔===; group substitution; Re and R? each independently represents a hydrogen atom or a methyl group; R9 is a hydrogen atom, a dentate atom, or a methyl group, an ethyl group, a scorpion, a bite ketone or Pyridyl, the pyridyl group is unsubstituted or substituted with a Ci_C2 alkoxy group, or when Y is a group 9 , two adjacent groups together with the carbon atom to which they are attached may form a benzene ring; R8 together with R5 And the nitrogen atom bonded to R5 together forms the 14-diazepan-1 -yl group, or R8 is a hydrogen atom, or a straight or branched chain Ci_C5 alkyl group, cyclohexyl group, adamantyl group, piperylene Piperidine , 10, phenyl, -(d-Cd)-cyclohexyl, _(Ci_C5^h(c:"25 alkoxy), -A-SOrR, -AA, -ALC(0)NR , R&quot;, -AL-CN, -AC(0)-N(CrC2 alkyl)_l_cn, _A-C(0)-NR'R',, -AC(0)-AM &gt; -AC(0) -R&quot;' &gt; -A-C02-R* &gt; -AC(0)-L-Am &gt; -AC(0)-L-CN or -AC(0)-L-〇-R, group Wherein R, and R, are the same or different and each represents an atom, or a straight or branched chain, and R"' represents a straight or branched chain Cl_C5 alkyl, CrC2 halo or Ci_Cd alkyl The ring e group, the adamantyl group, the hexanyl κ group, and the group are unsubstituted or substituted by #素轩 or hetero, linear or branched Ci_c2 alkyl or Q-C2 alkoxy, and wherein L is straight Chain or branched chain Ci_Ch_alkyl, 478 201130835 A is piperidinyl or oxaridinyl 'unsubstituted or substituted with Ci_C2 alkyl, A' is phenyl or acridinyl, unsubstituted or oxime Or substituted with 2 halogen atoms or a CN group, A&quot; is pyrrolidinyl, pyridyl, pyrazolyl or cyclopropyl, the pyrrolebital group, the ratio of the bite group, the alpha ratio to the sial group and the cyclopropyl group Replace or pass 1 or 2 halogen atoms or cyano groups are substituted, and hydrazine is an imidazolyl group. 24. The compound for use as described in claim 1 or 2, which is one of the following: 3-(4_{[ (lS)-l-phenethyl]amino}purine_2·yl)imidazo[l,2-a]D-pyridyl-6-phthalonitrile; 3-(4-{[(lR)-l -Phenylethyl]amino}pyrimidine_2·yl)imidazo[ua] 0 is more than -6-indene nitrile; 3-[4·(benzylamino)-n-butyl-2-yl] oxazole [1,2-punching ratio biting _6. carbonitrile; 3-(4-{[(15&gt;2-decyloxy-1-indolylethyl]amino}pyrimidin-2-yl) oxazolo[ 1,2-α]pyridine-6-phthalonitrile; 3-{4-[(cyclohexyl)amino]pyrimidin-2-yl}imidazo[ι,2-α]pyridine-6-phthalonitrile; 3-{4-[(2-methoxyethyl)amino]methicin-2-ylpyrazole[l,2-fl]acridine-6»carbonitrile; β 3·{4_[(1 -adamantylmethyl)amino]pyrimidin-2-yl}imidazo[1,2-β]pyridine-6-carbonitrile; 3-{4-[(2,2-dipropyl)amino group Pyrimidine_2_yl}indazole and [ι,2_α]pyr 479 201130835 bite-6-method, 3-{5-bromo-4-[(2,2-dipropylpropyl)amino]pyrimidine -2-yl}imidazo[1,2-β]αι^α定-6-曱 guess, 3-{4-[(2,2-dimercaptopropyl)amino]-5-0 base- 1 - base 0^σ定-2-yl} mouth rice 0 sit and [1,2-8] ° bite _6-carbonitrile; 3-[4-[(2,2-dipropylpropyl)amino group ]-5·(2-decyloxyacridin-4-yl)pyrimidin-2-yl]-salt and [1,2-&]° ratio 11 -6-曱 guess, 3-[4- [(2,2-diisopropyl)amino]-5-(2-o-oxy-1,2-dihydropyridin-4-yl)pyrimidin-2-yl]imidazo[1,2-a ] acridine-6-carbonitrile; 3-{4-[(2,2-dipropylpropyl)amino]-5-0 is more than a bite-3-yl-mouth-2-yl} [1,2-a]0 than bite-6-carbonitrile; 3-{4-[(3-fluorophenylindenyl)amino]pyrimidin-2-yl}imidazo[1,2-a]acridine -6-carbonitrile; 3-{4-[(4-fluorobenzyl)amino]pyrimidin-2-yl}imidazo[1,2-α]acridin-6-carbonitrile; 3-{4 -[(2-mercaptophenyl)amino]pyrimidin-2-yl}imidazo[1,2-α]吼 bit-6-method; 2-({[2-(6-cyanoimidazole) And [1,2-α]acridin-3-yl)pyrimidin-4-yl]amino}methyl)piperidine-1-carboxylic acid tert-butyl ester; 3- (4-{[(1-ethylhydrazine) Isopiperidin-2-yl)indolyl]amino}pyrimidin-2-yl)imidinary sigma[1,2-α]0 is more than -6, phthalonitrile; 3-[4-(tetrahydro-2) //-piperazin-4-ylamino)pyrimidin-2-yl]imidazo[l,2-fl] 0 is compared to 唆-6-曱 guess, 3-(4-(8-murine 焼克焼&gt; -4-ylamino)♦ Bite-2-yl) taste σ sit and [l,2-a] 480 201130835 pyridine-6-carbonitrile; 3-[4-(cyclohexylamino)pyrimidin-2-yl]11-moxazolo[1, 2-α]pyridine·6-indene nitrile; 3-{4-[(trans-4-hydroxycyclohexyl)amino]]-pyridin-2-yl}imidazo[ng pyridine-6-indoleonitrile; 3-{ 4-[(5-Pyridyl-2-adamantyl)amino] mocking-2-yl} miso and [1,2·ίζ]π than bite-6-a guess; 3-{4-[ (5-carbyl-2-adamantyl)amino] 咬 -2--2-yl} 咪 α sit and [1,2-β] σ than bite -6·曱 guess; 2- {4_[(2, 2·Dimethyl propyl)amino]quinazolin-2-yl}imidazolium 0 to -6-indoleonitrile; 3-{4-[phenylhydrazino(methyl)amino] pyridine base Isozo[2]pyridin-6-carbonitrile; 3-(4-{[(l*S&gt;l-phenethyl)amino}- </ RTI> </ RTI> oxazolidine [1,2 _ 冲比 bit-6-formic acid; 2-(6-fluoroimidazo[i,2-a]pyridine_3_yl) good [(6) small stupid ethyl]pyrimidine-4-amine; anti-4-{ [2-(6-fluoroimidazophthyl p, 2 core]pyridine-3-yl)pyrimidin-4-yl]amine} cyclohexanol; ^ ΜΗΙΧ2^1,7^)-5-trans-base-;2-金 院 ] 胺 胺 胺 胺 胺 胺 胺 胺 胺 1 1 1 1 1 1 1 [1,2-α]pyridine·6-carbonitrile; α]pyridine_3_ylpyrimidine _4_amine; #-(2,2-dimethylpropyl)-2-imidazo[l,2-fl]pyridin-3-yl-6-pyridin-3-ylpyrimidin-4-amine; 481 201130835 3- (6-{[(15)-1-Phenylethyl]amino}吼嗓_2_yl) 〇米0 sits and [1,2_ 比 啶 -6 -6 曱 曱 ; ;; 3·{6-[ (cyclohexyl)amino] 咐 &lt; azine-2-yl} imidazopyridin-6-phthalonitrile; 6-(6·fluoroimidazo[1,2_α]pyridine_3_yl)-Α4 ( 15&gt;1-Phenylethyl]«bi-2-amine, 6-(6-azamidazo[l,2-fl]&quot;bipyridin-3-yl)-Α4(15&gt;1_phenethyl ].嘻-2-amine; (5)-0-(°米嗤[l,2_a]0 is more than _3·yl)-N-(l-phenethyl)d than 嗓-2-amine; 6 -(6-cyclopropylimidazo[1,2-&lt;a]pyridin-3-yl)[[1-1-phenethyl]pyrazin-2-amine; 7V-[(15)-1- Phenylethyl]-6-(6-0 is more than -3-ylimi "Sit and [1,2-〇]» than 唆-3-yl) B is more than 嘻-2-amine; 7V~[(1» S)-1-Phenylethyl]-6-(6-0 than biting-4-yl π m salido[ι,2·β]π ratio α--3-yl)nl:b^-2-amine Λ4(1-Phenylethyl H-[6-(1open-n-biazole-4-yl). Mizozo[1,2-α] π ratio bite_3-yl]α ratio β Qin-2 -amine, phenethyl]-6-(6-phenyl-sodium sulphate [1,2-- _ _3-yl) pyrazin-2-amine; 6-[6-(4-fluorophenyl) σ米唑和[1,2-小比啶_3_基]#[((6)小苯乙]β比嗓-2-amine, 3_(4_{[(3 外一 1-(ethanesulfonyl)) Piperidine·3-yl]amino}pyrimidine_2-yl)imidazo[1,2·α]pyridine-6-carbonitrile; 482 201130835 3-(4-{[(3 and)-1-(iso)丙 醯 ) ) 旅 旅 ) ) ) ) ) 旅 旅 旅 旅 旅 旅 旅 旅 旅 旅 旅 旅 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾 唾And)-1-(cyanoethyl fluorenyl) succinyl _3_yl]amino) arginyl · 2 · yl) σ m 0 sit and [1,2-(3] ° than 唆-6-indoleonitrile ; 3-(4-{[ (3 and) -1- propyl-based brigade bite _3_yl] amine base} mouth bite-2_ base) mouth m α sit and [1,2-β]0 than bite-6-carbonitrile; 3- [4-({(3))-1-[(1·-ylcyclopropyl)carbonyl]α bottom biting_3_yl)amino)pyrimidin-2-yl]imidin[1,2-external Specific bite-6-indene nitrile; 3-(4-{[(3 and)-1-(decyloxyethyl) π 咬 _3_ yl] aminyl} mouth bite_2_ carbazole [1,2·α]pyridine-6-phthalonitrile; 3-(4-{[(3 and)-1-(3-hydroxy-3-methylbutanyl) brigade ·3_yl]amino} spray 0定-2-yl)π米嗤[1,2-〇]° ratio biting-6-indene nitrile; 3-(4·{[(3 and)·1-(3,3-dimercaptobutyl) Piperidine·3—yl]amino} 喊 -2--2-yl) imi ng [1,2-&lt;3]° ratio bite-6-carbonitrile; 3-(4_{[(3 and)- 1-(1/ί-ρ米嗤和1_4_基乙基)〇 bottom bite_3_yl]amino}pyrimidin-2-yl)imidazo[1,2-α]pyrodo-6-曱Nitrile; Η4_({(3)) small [(5-cyanopyridine_2_yl)]anthracene}amino)bitid-2-yl]0 m嗤[1,2-〇] 0 to bite-6-carbonitrile; 3-(4-{[(3Λ)-1-(3,3,3-trifluoropropenyl) brigade ·3_yl]amine-based base-2-) Imido[1,2-α]0 is a bit of -6-indoleonitrile; (3Λ), 3-{[2·(6·cyanosoxazolyl)}-Agv-dimercaptopiperidine-1 -A Indoleamine; 3-{4-[((3)-{{light, phen-2-yl-pyranyl), piperidinyl)amino]pyrimidin-2-yl}. Mizozo[12·"]pyridine_6_phthalonitrile; 483 201130835 3-(4-{[(3i?)-l-(5-cyanoacridin-2-yl)piperidin-3-yl] Amino}pyrimidin-2-yl)indolizine[1,2-&lt;3]« is more specific than 1,4--6-indene nitrile; 3-(4-{[(3 magic-1-(4-cyano) 2-fluorophenyl)piperidin-3-yl]amino}pyrimidin-2-yl)-salt and [1,2-&lt;3] bite-6-carbonitrile; 3-{4-[[ (37?)-1-(cyanoacetamido)piperidin-3-yl](methyl)amino]pyrimidin-2-yl}imidazo[1,2-α]0 ratio bite-6 - phthalonitrile; 3-(4-{[(35)-1-(cyanoethinyl)piperidin-3-yl]amino}pyrimidin-2-yl) °m 0 sit and [1,2- α]π 唆-6-indene nitrile; Chuanren-3-(4-{1-(gas-based ethyl)-4-methyl σ -3--3-yl]amino} guan-2- Imidazo[1,2-α]acridin-6-indolecarbonitrile; cis-3·(4-{1 -(ethylenyl)-4-mercapto-3-yl]amino] Αα定基)σ米0 sits and [1,2-β]° ratio 唆-6-phthalonitrile; 3-{4-[[1-(ethanesulfonyl)-4-mercaptopiperidin-3- ]](fluorenyl)amino]pyrimidin-2-yl}0 m spit [1,2-〇]0 than bite-6-indene nitrile; 3-((3i?)-3-{|&gt; (6-fluoroimidazo[1,2-α]acridin-3-yl)pyrimidin-4-yl]amino} dentate-1-yl)-3-oxo-propion, (7?)- 1 -(3-(2-(6-say p mπ sit and [ 1,2-a]α is more than β--3-yl), biting 4-amino-amino)piperidine-1-carbonyl)cyclopropanecarbonitrile; 2-(6-fluoroimidazo[1,2-« Acridine-3-yl)--[(3,3-(3,3,3-trifluoropropanyl) 11 -3-yl] octa-4-amine; 2-(6- Flutimidazo[1,2w]pyridin-3-yl)-A4(3i?)-1 -(1//-pyrazole_4yl tracing) Ninja -3-yl] mouth bite-4-amine, ( Cyanomethyl)-3-{[2-(6-fluoroimidazo[l,2-fl]acridin-3-yl)pyrimidin-4-yl]aminomercaptopiperidin-1-ylamine ; 484 201130835 2-((3i?)-3-{[2-(6·Fluoroimidazo[ι,2-bromopyridin-3-yl)carin-4-yl]amino}π辰 bite- 1-yl)-2-methylpropanamide; 2-(6-fluoroimidazo[ι,2_α] π-pyridin-3-yl)-methyl-#-[(3 and)-1-(3 ,3,3-trifluoropropionyl)piperidine-3-ylpyrimidine-4-amine; (Α)·3-(3-((2·(6-fluoroimidazo[1,2-a]] Acridine-3-yl)pyrimidin-4-yl)(indenyl)amino) "indolyl-1-yl)_3_ pendant oxypropionitrile; (illusion-1-(3-((2-(6) -fluoroimidazo[ua] σ-pyridyl_3_yl)pyrimidin-4-yl)(fluorenyl)amino) "Bottom-Butyl-1-yl"cyclopropanonitrile; 3- ((3 and)_3 - {Ethyl [2_(6_fluoroimidazo[!,2_4pyridine-3-yl)pyrimidin-4-yl]amino}pyridin-1-yl)_3- Propionitrile group; W is ethyl-2- (6-fluoro-imidazo [IJW] pyridin _3_ yl) - do [(3 and) -1- (3,3,3-trifluoro-propan-acyl). Bottom bite _3_基] shouting 44_amine; 3-((3 and)-3-{(cyclopropylmethyl)[2_(6-fluoroimidazo[inhibition of pyridyl) pyrimidine-4 -yl]amino}piperidinyl-i-yl)_3_sideoxypropionitrile; AK cyclopropenyl)-2-(6-fluoroimidazo[ι,2_α]acridin-3-yl)-Λ4 From)-1-(3,3,3-trifluoropropionyl)piperidine-3-yl]pyrimidine_4_amine; 3-((3 and)_3·{[5_fluoro·2-(6 -Fluoroimidazo[ugyridin-3-yl)pyrimidine_4_yl]amino}α-bottom-1-yl)_3_sideoxypropionitrile; 5-fluoro-2-(6-fluoroimidazolium [丨,^] „比啶-3·基)善[(3;?)-1-(3,3,3_trifluoropropenyl)pyrazine·3_yl]carcinyl -4-amine; 3-((3/?)"3-{[2_(6-Fluorine and rushing than biting _3-yl)·5-methyl, guanidin-4-yl]amino}Nanylpyridinyl) _3-Sideoxypropionitrile; 2-(6-fluoro 0 m salido [1,2-闰0 to σ定_3_基)_5_曱基善[(3和)-1-(3,3 , 3-di-propanyl propyl group) 0 唆 ____ base] ringing _4_amine; 485 201130835 3-((3 and)-3-{[2-(6-fluoroimidazo[[, 2, ·β]pyridine_3_yl)pyrimidine_4_yl]amino}pyrrolidin-1-yl)-3-oxopropanenitrile; 3-{4-[4-(cyanoethenyl)· 1,4-diazacycloheptane_丨_yl]pyrimidine_2_yl}°m.[1,2-&lt;3]° ratio bite-6-A ; 3-((3Λ)-3_{[5-Gas-2-(6-fluoroimidazopyridin-3-yl)pyrimidin-4-yl]amino}-------------------- Oxypropionitrile; 3-((3 and)-3-{[2-(6-fluoro-methane-[1,2-α]吼-3-yl)-biting _4_yl] Amino }α辰唆-1-yl)-2,2-dimercaptopropy; 2_((3/?)_3-{[2-(6-fluoro-[s)-[s,][1,2_α]η than bite- 3-(6)-amino-piperidin-1-yl)acetamide; (S)-2-(6-fluoroimidazo[l,2-a]acridin-3-yl -N-(l-(5-fluoropyridin-2-yl)ethyl)pyrimidine-4-amine; 2-(6-fluoroimidazo[l,2-a]0 is indole-3-yl)- Ν_(»Bite-2-ylmethyl)pyrimidine-4-amine; (S)-2-(6-fluoroimidazo[1,2-a]acridin-3-yl)-indole-(1- (4-fluorophenyl) butyl)pyrimidine-4-amine; (R)-3-(2-(6-fluoroimidazo[l,2-a]pyridin-3-yl)pyrimidin-4-ylamine ))-1-propylpyrrolidin-2-one; 6-fluoro-3-(4-(2-(° bit -2-))D ratio slightly -1-yl) carcinoma-2-yl Miso-[l,2_a]pyridine; (S)-N,N-diethyl-1 -(2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-4 -yl)pyrrolidin-2-indoleamine; (R)-N,N-diethyl-1 -(2_(6.fluoroimidazo[1,2-a]acridin-3-yl)pyrimidine- 4-yl)pyrrolidin-2-yl Guanamine; 486 201130835 2-((lr,4r)-4-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamino)cyclohexyl) Acetonitrile; (R)-2-(3-(2-(6-乱°米ββ[1,2-a]atb 唆-3-yl) mouth -4-amino group) - keel yellow base) B guess, (R)-4,4,4-trifluoro-1 -(3 -(2-(6-fluoroimidazo[1,2-a]acridin-3-yl) Carcinoxime-4-ylamino)α-chenid-1-yl)but-1-indole, ((R)-3-(2-(6-fluoroimidazo[1,2-a]acridine- 3-(yl)pyrimidin-4-ylamino)piperidin-1-yl)((lR,2R)-2-phenylcyclopropyl)anthone; (R)-1 -((R)-3- (2-(6-fluoroimidazo[1,2-a] «bipyridin-3-yl)pyrimidin-4-ylamino) brigade _1_yl)_2_radio-3,3-di Butyl-1-yl, (R)-2-cyclopentyl-1-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidine-4 -aminoamine) brigade-1-yl) acetamidine, (R)-l-(2-(3-(2_(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidine -4-ylamino)piperidin-1-yl)-2-oxoethyl)-5-methylpyrimidine-2,4(1H,3H)·dione; (R)_l -(3- (2-(6-gas ° σ sit and [1,2-a] ntb -3-yl) gnach-4-ylamino)piperidin-1-yl)-2-(1Η-1, 2,4-triazol-1-yl)ethanone; (R)-(3-(2-(6-) Flutimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)(1-indolylcyclohexyl)anthone; (2,2-difluoro Cyclopropyl)((1〇-3-(2-(6-fluoroimidazo[1,2-micropyridin-3-yl))-indolyl-4-ylamino)α-inden-1-yl) Hyperthyroidism, ((R)-3-(2-(6- disorder 13 m β sita[1,2-a]π than -3-yl) ♦ ate-4-ylamino) piperidine-1 -())((lR,2S)-2-hydroxycyclopentyl)methanone; (R)-l -(3-(2-(6-乱°米米坐和[1,2-a] ntb bite -3-yl) gnaca-4-ylamine 487 201130835 base acyl-1-yl)-2-(1 Η-pyrazole small) ethyl ketone; (R)-cyclohexyl (3-〇(6- Flumimidazo[^a]pyridin-3-yl)-naphthyl-4-ylamino)[alpha]-biting&gt;1-yl)carbazide; (R)-(3-(2_(6-fluoroimidazolyl), 2_φ pyridine _3_ group) 啶 _ _4 ylamino) piperidin-1-yl) (4-methyl-1,2,3 "sedazol-5-yl) ketone; (8)-1_ Bismuth(2-(6-fluoroimidazo[丨,2♦pyridinyl)pyrimidin-4-ylamino)pi--1-yl)-2-(4-(methyl)phenyl)ethanone; (8) small ((8) W6-fluoroimidazo[1,2♦bipyridin-3-yl)- phenanthridin-4-ylamino)) bottom bit-1-yl)_3_phenylbutan-1-one; (8)-1 -((R)-3-(2-(6-fluoroimidazo[!,2_a] „ than bite-3· ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) , 2_a]n than bite _3_ base) cough icylamino) brigade-1-yl)-3-(4-decyloxyphenyl)propanone; (R)-(5-fluoro- 2,6-dihydroxypyrimidine·4_ylindole 3_(2_(6-fluoroimidazo[l,2-a]° than indole-3-yl) mouth bit-4-ylamino) piebitate + base)曱Ketone; (8)-2-(3·gas benzene AH_((R)_3_(2_(6·4 and [丨, 2 a] π ratio bit _3_yl) pyrimidinyl) piperidine·丨-yl )·)-hydroxyethyl ketone; (RH3-(2-(6|mastatin D, 2♦ than biting _3_yl)) _4 ylamino) piperidin-1-yl) (pyrimidine-5- Methyl ketone; (RM3-(6L sitting and [U♦ 岭3 piperidine_1_yl XH trifluoromethyl)cyclobutyl)methanone; piperidin-1-yl) (1-hydroxyl Cyclopropyl)methanone; (8)-2-(benzyloxy) small (3_(2_(6 fluoro-salt and like but biting winter base) 201130835 啸 '7-1,4-amino group) 1^_ Bite-1-yl)acetamidine, (R)-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino) 1-based) (1Η-α-induced 0-2-yl)-methyl, (R)-l-(3-(2-(6-乳°米α坐和[1,2-a]atb bite- 3-yl) cancer bit -4-ylamino) nanny bit-1-yl)-5-(4-phenylphenyl)pent-1- , (R)-2-(2-chlorophenyl)-1 -((R)-3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl) shouting 11 -4-ylamino) brigade-1-yl)-2-ylaminopurine, (R)-l-(3-(2-(6-fluoroimidazo[l,2-a]acridine- 3-()pyrimidin-4-ylamino)piperidin-1-yl)-2-(decylamino)ethanone; (R)-l-(3-(2-(6-fluoroimidazo[1] , 2-a] acridine-3-yl)pyrimidin-4-ylamino) σ chen-1-yl)-2-(2-decyloxyethoxy)ethanone], (R)-l -(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino) brigade-1-yl)-2-(2.-曱(R)-(3-(2-(6-fluoroimidazo[l,2-a]-oxaridin-3-yl)pyrimidin-4-ylamino) 0 0 0 定-1-yl) (tetrakis-2Η-α-Chen-4-yl) fluorenone; (R)-l-(3-(2-(6-fluoroimidazo[1,2-a] Acridine-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)-2-(2-methyl-1H-benzo[d]imidazo-l-yl)ethanone; 3-(R)-3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyridin-4-ylamino) brigade-1-yl曱嗣, (R)-N-(2-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino)α σ定_1_基)_2&gt; side oxyethyl)-N-mercaptobenzamide, (R)-2-(3-chlorophenoxy 1-(3-(2-(6-fluoroimidazo[1,2-a]acridin-3-yl)pyrimidin-4-ylamino)piperidin-1-yl)ethanone; R)-l-indole (2-(6-fluoroimidazo[l,2-a]acridin-3-yl)pyrimidin-4-ylamine 489 201130835 〇) 〇 咬-1-yl)_2,2 _双(曱曱基)丁小_ ; (R)-l-(3-(2-(6-fluoroimidazo[l,2-a]n-pyridin-3-yl))) Amino)0 bottom bite-1_yl)-2-(2H_tetras-5-yl)B-; N-(1 -(1 Η-1,2,4-triazol-3-yl)piperidin (3-(2-(2-(6-fluoroimidazo[l,2_a])pyridine -3-yl)pyrimidin-4-ylamino)piperidin-1-yl)thiazole-5·phthalonitrile; (R) -1 -((R)-3-(2-(6-fluoroimidazo[ , 2_a]pyridine-3 _yl)pyrimidine _4_ylamino) D-Chenyl-1-yl)-2,3-dihydroxypropan-i-one; (S) -1 -((8)-3 -(2 -(6-fluoroimidazo[1,2-a]acridazol-3-yl)pyrimidin-4-ylamino)bristin-1-yl)-2,3-dihydroxypropan-1-one; (R -3-(3-(2-(6-fluoroimidazo[1,2-a]pyridine-3-yl)-5-methylpyrimidinyl))pyrrolidin-1·yl)-3 -Sideoxypropionitrile; (S) -2-(6-It imidazolyl)ethyl)-5-methylpyrimidin-4-amine; 2_(6_Fluoropyrene[1] 2_a]pyridine J _ group) loss _ ((5 _ pyridine pyridine 2 _ group) sulfhydryl) mouth bite-4,5-diamine; 2_(6-fluoroimidol [l, 2_a] pyridinyl (10)^Book Hydroquinoline-5-yl)-biting-4,5-diamine; (R)-2-(6-fluoroimidazo[1,2-a] η-pyridyl_3_yl)_Ν4 · (3_methylbutan-2-yl) mouth bite-4,5-diamine; 2-(6-fluoroimidazo[1,2-a]pyridine_3.yl)_Ν4_(^曱oxyprop-2- _ base) pyrimidine-4,5-diamine; 2-((lr,4r)_4-(5-amino-2_(6-fluoroimidazo[10) but pyridine group) pyrimidine 490 201130835 bite -4- Amino group) hexyl) B., (lr, 4r)-4-(5-amino-2-(6- scent π-s-mercapto) ♦ ate-4-ylamino)-1-methyl Cyclohexanol; 2-(6-fluoroimidazo[1,2-a]indole-3-yl)-N4-(l-(5-fluoroindole-2-yl)-2-indoleoxyethyl Pyrimidine-4,5-diamine; (S)-2-(6-fluoroimidazo[l,2-ap-pyridin-3-yl)-4-(1-(5-fluoroacridin-2-) Ethylaminopyrimidine-5-carboxylic acid; (S)-2-(6-gas °m π sitting and [1,2-a] ntb -3-yl)-4-(1 -(5- Gas Dtb bite -2_yl)ethylamino)pyrimidine-5-decylamine; (S)-2-(6-gas 0 m π 圭[1,2-a] *° ratio σ定-3 -yl )-4-((1 -(5 - gas 1 ° ratio bit-2-yl)ethyl)(methyl)amino)pyrimidine Pyridin-5-formic acid; 2-(6-fluoro 0 m sigma and [l,2-a]n than -3-yl)-4-(indole ratio -3-ylmethylamino)pyrimidine-5 -formic acid; 2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-4-(acridin-3-ylmethylamino)pyrimidine-5-carboxamide; 2-( 6-fluoroimidazo[1,2-a]acridin-3-yl)-4-((5-fluoroindol-2-yl)nonyl)pyrimidine-5-decanoic acid; 2-(6 -fluoroimidazo[1,2-a]pyridin-3-yl)-4-((5-fluoropyridin-2-yl)nonylamino)pyrimidine-5-decylamine; (S)-2-( 6-fluoroimidazo[l,2-a]acridin-3-yl)-4-(1-(4-fluorophenyl)butylamino)pyrimidine-5-decanoic acid; (S)-2-( 6-fluoroimidazo[1,2-a]acridin-3-yl)-4-(1-(4-fluorophenyl)butylamino)pyrimidine-5-decylamine; 4-((lr, 4r)-4-(cyanoindolyl)cyclohexylamino)-2-(6-fluoroimidazo[1,2-a] 491 201130835 pyridin-3-yl)pyrimidine-5-decanoic acid; 4-( (lr, 4r)-4-(cyanoindolyl)cyclohexylamino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-5-carboxamide; (R)-2,2-dimercapto-1,3-dioxol-4-yl)((R)-3-(2-(6-fluoroimidazo[l,2-a) ] «Bipyridin-3-yl)-5-methylpyrimidin-4-ylamino)piperidin-1-yl)indanone; (R)-l-((R)-3-(2-(6) -fluoroimidazo[l,2-a] 3-yl) -5-α given cancer Yue-yl 4-ylamino) trip. Di-1-yl)-2,3-dipyridin-1-one, (R)-3-(3-(5-amino-2-(6-fluoroimidazo[l,2-a) Acridine-3-yl)pyrimidin-4-ylamino)-3-oxo-propyl gamma, (R)-3-(3-(5-cyclopropyl-2-(6-fluoroimidazolyl) [l,2-a]Acridine-3-yl)pyridin-4-ylamino)Budgen-β-l-yl)-3-oxo-propion, (R)-4-(l-( 2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[l,2-a]n than -3-yl) mouth bite-5-曱 guess, ( R)-3-(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-5-(nonylsulfonyl) ♦ π-1,4-amino group)咬--1-yl)-3-oxo-propanoid, (R)-4-(1-(2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoro Imidazo[1,2-3·]πιΐ&lt;^-3-yl) mouth bite-5-formic acid ethyl ester, (R)-4-(l-(2- disordered ethyl aryl) brigade π-ding-3 -ylamino)-2-(6-disorder σm0-iso[1,2-a]pyridin-3-yl)pyrimidine-5-decanoic acid; (R)-4-(1-(2-cyanide) (Ethyl)piperidin-3-yl,amino)-2-(6-fluoroimidazo[1,2-a]pyridin-3-yl)pyrimidine-5-carboxamide; (R)-3 -(3-(2-(6-fluoroimidazo[l,2-a]acridin-3-yl)-5-methoxypyran-4-ylamino)). -3- Side Oxygen C., 492 201130835 (R)-3-(3- (2-(6-fluoroimidazo[l,2-a]&quot;bipyridin-3-yl)-6-(1H~i,24-triazol-1-yl)-cyano-4-ylamino) Piperidin-1-yl)_3_sideoxypropionitrile; (R)_3-(3-(2-(6-fluoroamido[l,2-a]»pyridin-3-yl)-6 -(4-fluorenyloxazin-1-yl)pyrimidin-4-ylamino)piperidin-1-yl)_3_sideoxypropionitrile; (R)-3_(3_(2_(6-1) Isozo[1,2-a;h-pyridin-3-yl)-6-(piperidinyl, 1 yl)-pyridylamino) bistidin-1-yl)-3-oxopropanenitrile (8)-3-(3-(2-(6-Fluoropropylidazo[1,2-a].pyridin-3-yl)-6-(4-(indolyl)piperazine-1 -yl)pyrimidin-4-ylamino)piperidin-1-yl)-3-oxo-propion; (R)-3-(3-(2_(6· 咪α坐和[1,2- a] ° ratio σ -3- group)-6-(&gt;^%% base) gnach-4-ylamino group) brigade bite_1_yl)_3_sideoxypropionitrile; (R)- 3-(3-(6-(didecylamino)-2-(6-fluoroimidazo[1,2-a]° pyridine yl) aceton-4-ylamino) (3) 3-(oxy)propanonitrile; (R) -3-(3-(2-(6-fluoro-[sigma][[,,,,,,,,,,,,,,,,, (2-〇sf·morpholinyl)ethylamino)pyrimidin-4-ylamino)piperidinyl)-3-oxopropanenitrile; (8)-3·(3-(2-(6-fluoro) p 米嗤[l,2-a]n than -3-yl)-6-(2-methoxyB Amino)pyrimidin-4-ylamino)piperidinyl-1-yl; pendant oxypropionitrile; (S)-l-(6-((R)-1-(2-cyanoethenyl)piperidin Pyridin-3-ylamino)-2-(6-gas-mouth saliva[l,2-a]a is more than -3-yl) squirting ·4_yl) "Bihabite-2-carboxylic acid; R)-3-(3-(2-(6·fluoro^米° sits and [i,2_a]n is more than -3-yl)-6-methoxybend-4-ylamino) brigade bite -1-yl)-3-oxo-propanonitrile; (R)-3-(3-(2-(6-Gas)[i,2_a]v* than indol-3-yl)-6 -(2-(〇比略 bit-1-yl)ethoxy) mouth biting _4·ylamino)π辰咬小基)_3-lateral oxypropyl guess; (R)-3-(3- (2-(6-Fluorozolo[1,2_a]α-pyridin-3-yl)-6-(2-(indolyl-morpholinyl)ethoxy)pyrimidin-4-ylamino)piperidine _丨_yl)-3-sided oxypropionitrile; 493 201130835 (R)-3-(3-(2_(6-fluoroimidazo[l,2-a]« pyridine·3·yl)_6- (2-methoxyethoxy) shouting 4-ylamino) β-n-yl-1-yl)-3-oxo-propanonitrile; (R)-6-(1-(2-cyano) Ethyl)amino-3-ylamino-2-(6-fluoroimipiro[l,2-a]pyridin-3-yl)pyrimidine-4-carbonitrile; (R)-3-( 3-(2-(6-fluoro). Mizozo[1,2-a] η-pyridin-3-yl)-6-(2H-tetrasyl-5-yl)cyclopyridine-4-ylamino)pyridin-1yl)_3_ side Oxypropionitrile; (R)-3-(3-(2-(6-fluoroη米唾和[1,2-江]°比咬-3-基)-6-(1-mercapto-1H) - 四哇-5-基) 啶 啶 基 胺 ) 旅 旅 旅 ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) , 2_&amp;]〇1»定_3_基)_6_(2_methyl-2Η-tetrazol-5-yl)pyrimidin-4-ylamino)piperidine 丨-yl) pendant oxypropionitrile (R)-6-(l-(2-cyanoethyl)piperidinyl-3-ylamino)_2_(6·fluoroimidazo[l,2-a]nfc^-3-yl) mouth Bite _4_carboxylic acid; , (R)-6-(1 _(2-cyanoethyl)piperidin-3-ylamino)-2-(6-fluoroimidazo[l,2_a]n ratio Bite _3_ base), bite _4_carbamamine; (R)-3-(3-(6-amino-2-(6-fluoroamido[1,2_a] B-pyridin-3_ )))-4-ylamino)pyridinyl)-3_sideoxypropionitrile; (R)-3_(3-(5-fluoro-2·(6·fluoroimidazole, 2·small)比 _ 3 _ _ _ _ _ _ _ _ _ _ _ _ _ _ -4- 基 基 基 基 基 ) ) ) ) ) ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ·Fluorine 2_(6·Fluoropyre-Ha]pyridyl-based)-6.----------------------------------------------------------------------- ; ^)-3-(3-(2-(6-fluoroimidazo[[,^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ - 3 - pendant oxypropionitrile; or a pharmaceutically acceptable salt or solvate thereof or a cerium-oxide or 494 201130835 stereoisomer, as described in any of the claims For the use of chemical conversion is carried out by the inhibition of __. The object, which is the household /, ^ 凊 凊 凊 凊 凊 凊 供 供 my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my my Diseases and travel diseases, , and &amp; transplant rejection; and immune-mediated, W*: pathological conditions or diseases are selected from inflammatory diseases. K (5) ^ Patent Fan ^ 26 For the use of a compound, which is a sputum, a sputum, or a disease selected from the group consisting of a sputum proliferative disorder, a white blood sputum disease, and a solid tumor, and wherein the treatment is performed by inhibiting the genus 28. The compound for use according to claim 27, wherein the pathological filament or disease is selected from the group consisting of bone marrow and a transplant rejection, and an immune-mediated disease. Or wherein: said recording pathology or disease is selected from inflammatory diseases. 29. The compound for use according to any one of the patent claims, wherein the pathological condition or disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis (cafe &amp;amp); sci_is ), inflammatory bowel disease, dry eye, lysine, allergic conjunctivitis, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), atopic dermatitis, and psoriasis. 30. An fflit of a compound as claimed in any one of claims 1 to 24, which is exemplified for the manufacture of a medicament for the treatment of a patent such as Cap No. 495 201130835 item 1 or item 25 to the disease. 1d to the pathological condition of the coating or An agent that inhibits the disease of the Janus kinase of an individual in need thereof. Pathology as defined in any one of the items = as described in the therapeutically effective amount of the compound as described in the Patent Application No. W No. L = or any of the claims A pharmaceutical composition of a compound as described herein and a pharmaceutically acceptable diluent or carrier. 33. A compound of the formula (I) or a pharmaceutically acceptable salt or solvate thereof or an N-oxide or a stereoisomer or a deuterated derivative, 1 ^ (Formula I) wherein m, X, Y and R! to % are as claimed in claim 496 201130835 to item 24, wherein the compound is not: 6-imidazo[1,2- a]pyridine_3_yl_team (3]1)_3_piperidinyl-2-pyrazinamine hydrochloride; 6-mouth rice bran[l,2-a]° than bit-3-yl- N-(3S)-3-pyranyl-2-n-pyrazineamine; 6-(6-azamidazo[1,2_a]pyridine-3-yl)_N_(3R)_3·piperidinyl_2_pyridyl Azinamide; 6-(6-methoxyimidazo[1,2-micropyridyl-3-yl)_N_(3R)_3·piperidinyl-2·pyrazinamine; 6 嗤米嗤[l, 2-a]pyridin-3-yl-N-(3R)-3-pyrrolidinyl-2-pyrazinamine; ', Ν-(4,4-fluoro-3-branched base)-6-mi嗤[l,2-a]DJt^-3-yl-2-β-pyrazinium hydrochloride; 6-imidazo[l,2-a]pyridin-3-yl-N-[(3R,4R )-4-methyl-3-pyrrolidinyl]-2-Ditn-heptylamine; N-(3R)-3-0 is more than butyl-6-[6-(trifluoromethyl)-m-α [i,2-a]n is more than indole-3-yl]-2-npyrazine; α,α-monomethyl-3-[6-[[(3R,4R)-4·methyl-3_π Bilobityl]amino]-2-[rho] thiol]-imiphtho[1,24]° bit -6-sterol; 6-imidazo[l,2-a]pyridin-3-yl -3-methyl-N-(3R)-3-piperidine _2_ pyrazinamide; (2R,3R)_N_[6-(7-decyl imidazo[l,2-a]«pyridin-3-yl)-2.oxazinyl]_2-methyl-1 -azabicyclo[2.2.2]oct-3-amine; 3-isoxazo[l,2-a]°pyridin-3-yl-5-[(3R)-3-piperidinylamino] -2-n-pyrazinium nitrile citrate; 497 201130835 3-[6-[(3R)_3_派咬基基基]-2-0-pyrazinyl]_味σ sit[[,2_&amp;] 0-pyridine-7-carbonitrile; N-[(3R,5S)-5-(difluoromethyl)-3-indolyl]-6-imidazo[i,2-a] D ratio bite -3-yl-2-indenylamine; N-[(3S,4R)-4-fluoro-3-pyranyl]-6-p-miso-[l,2-a]° ratio -3- Keine-2-pyrazine; N-[(3 S,4S)-4-fluoro-3-bendylene]-6-flavored salino[1,2-a] ° ratio bite _3 -yl- 2-°-pyrazinium; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3S,4S)-4.methoxy-3·piperazyl]-2-° ratio Indoleamine; 6-imidazo[l,2-a]pyridin-3-yl-N-[(3R,6S)-6-methyl-3-piperidinyl]-2-pyrazinazine formate 6-Imidazo[1,2-a]pyridin-3-yl-N-[(3R,6R)-6-methyl-3-piperidinyl]-2-pyrazinazine formate; 6- [7-[2-(1·Methylethoxy)ethoxy]imidazopyridinyl-3-yl]-N-(3R)-3-Bentyl--2·°-p-amine; N -[(3S,4S)-4.ethoxy-3-piperidinyl]·6·imidazo[!,2-a]acridin-3-yl-2-pyramine; N-[( 3S, 4S) _4 · ethoxy "bottom bite _3-yl]-6- (taste and [l, 2a] 0 than bit-3-yl) pyridin-2-amine; 6-flavored saliva [ 1,2-a]pyridine·3-yl-3-indolyl-N-(3R)-3piperidinyl-2-pyrazinamine 2,2,2-trifluoroacetate; 6·(7-曱oxyimidazo[1,2-a] n-pyridyl-3(yl)-n-(3R)-3-piperidinyl-2-indole 0-methylamine; 498 201130835 6-(7-decyl taste Squat and [l,2-a]0 is more than -3-yl)-N-(3R)-3-Benbityl-2-pyrazinamine; N-(3R)-3-Bent bite-6 -[6-(Trifluoromethyl)pm0 sits and [l,2-a] 吼-3-yl]heptylamine; N-(3R)-3-Nandbityl-6-[7-( Trifluoromethyl) σ米嗤[l,2-a]〇 咬-3-yl]-2-decylamine; 6_(7-ethyl sigma-salt[l,2-a]0 ratio Benzo-3-yl)-N-(3R)-3-Bentyl-2-pyramine; 6-[6-(1-methylethyl)isoxazo[i,2-a]« Acridine·3·yl]_n_(3R)-3-indanyl-2-pyramine; 6_(7·chloroimidazo[1,2_a]pyridine_3_yl)-N-(3R)_3· Piperidinyl-2-pyrazinamine; N_[(3R,4R)-4-fluoro-3-pyrrolidinyl]_6-imidazo[i,2_a]pyridine·3·yl-2-pyrazinamine ; 6-[5-[(3-methyl-3-oxetanyl)methoxy]_111_benzimidazol-1-yl]-N-(3R)-3-pyranyl-2 - pyridazinamine; 6-miwa[1,2-a] bite-3-yl-N-(3S)-3-indolyl-2-ylamine; '6-(6- Methylimidazo[nypyridine-3-yl) N(3R)-34-rheptidyl-2·0-p-amine; 6-(7-methylimidazo[l,2-a]pyridine_3·yl] .N-(3R)-3-pyrrolidine X -2-pyridinylamine; soil•(7-methoxyimidazo[1,2 than bite_3_yl)_N_(3R)_3_D is more than pyridyl Alkylazine; ketone-2-499 201130835 N-(3R)-3-indenylpyridinyl-6-[7-(7-(trifluoromethyl)isoxazole and n,2_a]npyridin-3-yl]-2-pyridinium Azinamide; 6 m sit and [l,2-a]a than bitten-3-yl-N-(3-methyl-3-pyrrolidine)-2-π-pyrazinamine; 6-(6·A Oxyimidazo[1,2_a]pyridine-3-yl)-N-(3R)-3.pyrrolidinyl-2-pyrazinamine; 6-(7-ethylimidazo[1,2_a]pyridine_3· Base)_N_(3R)_34-rhodinyl-2-α ratio °qinamine; 6-[6-(1-methylethyl) oxazolo[pa]pyridine·3_yl]_n_(3R)_3_ 0 Each of the ketone amines; 6-mercaptomethylimidazo[l,2_a]pyridine _3_yl)_^_(3 magic _3_pyrrolidinyl-2-α decylamine; 6_(7_ clomiphene [l, 2_a ]n than bite · 3_ base (9) 70% is called fluin_3 pyrrolebityl]-2-pyridazinamine; N_[(3R,5S)-5_(fluoroindolyl)-3-indolyl]- 6-imidazo[l,2-a] 吼--3-yl-2-*^qinamine; N-[(3R,5S)-:5-(fluoroindolyl)_3_πpyrrolidyl]_6_[ 7_(Trifluoromethyl)imidazo[l,2_a]pyridin-3-yl]-2-pyrazinamine; 3-{6-[(3R)-piperidine-3-ylamino]pyridazine_2 _ } 味 味 并 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Azinamide; 6_(6-fluoroimidazo[l,2_a]pyridine-3-yl)_N_[(3R,6R) fluorenyl _3_ ketone group]-2-° guanamine; 500 201130835 N_[( 3R,5S)-5-(difluoroindolyl)_3_Dpyrrolidyl]_6_[7_(trimethylmethyl)imidazo[l,2-a]pyridin-3-yl]2-pyrazinamine; 6 -(6-fluoroimidazo[i,2_a]pyridin-3-yl)_N_[(3S,4R)_4 fluoro_3_pyrrolidinyl]-2-pyrazinamine; 6-(6-fluoroimipirin[ 1,2_a] D-pyridyl_3_yl)_N_(3R)_3吼pyridinyl•2-pyrazinamine; 6-(6-fluoroimidazo[i,2-a]pyridyl)_n_[(3S , 4S)-4-fluoro-3·pyrrolidinyl]-2-pyrazinamine; 6-(6-fluoroimidazo[1,2_a]pyridin-3-yl)_N-[(3R,6S)-6 -曱基·3-0辰2-ylpyrazine; 6-(6-fluoroimidazo[1,2-a] η than -3-yl)-N-[(2R,3R)-2-methyl-3-咬基基]-2-«»Biazinamide; 6-(6-fluorom-mazole[i,2_a]pyridin-3-yl)_n_[(2S,3R)-2-methyl·3-派咬基]-2-oxazinamide; 6-mouth rice saliva[i,2-a]n ratio bite _3·yl-Ν·(3·methyl π 洛洛 bit _3_ base) D ratio 嘻-2-amine; '6-imidazo[1,2-a]pyridin-3-yl-N-[(2S,3R)-2-indolyl-3-piperidinyl]-2-β-amine ; 6-(7-azamidazo[i,2-a]pyridin-3-yl)-N-[(2R,3R)-2-methyl-3-carboxylo]]pyridazinamine 6_(7·Azamidazo[l,2-a]pyridine-3-yl)-N-[(2.S,3R)_2-methyl-3·Becker base]-2-3⁄4 decylamine; 6-Miso-[l,2-a]D-pyridin-3-yl-N-[(2R,3R)-2-indolyl-3-piperidyl]-2-pyrazinamine; 501 201130835 N -(3R)-3_piperidinyl-6-[7-(2,2,2-trifluoro-1-methylethoxy)imidazo[l,2-a]^^-3-yl] -2-[p-azinamide; 6-fluorene-fluorene-(methoxymethyl)propoxy]isoxazo[l,2-a]pyrano_3_yl]-N-(3R)-3- a bottom bite base_2_π than guanamine; (lS,4R,6R)-N-(6-isoxazolo[i,2_a]pyridine_3_yl_2-pyrazinyl)_2_ azabicyclo[2.2.1 Geng-6-amine; (lS,4R,6R)-N-[6_(7-曱 口 口 η η η [i,2_a]0 唆 _3· yl)_2_ pyrazinyl]_2_azabicyclo[2.2.1 ]hept-6-amine; (1 S,4R,6R)-N-[6-(6-fluoroimidazo[1,2_a]pyridine each)_2_pyrazinyl]_2_azabicyclo[2.2. 1] hept-6-amine; 6-(7·chloroimidazo[l,:2-a]pyridine-3-yl)-N-[(3R,4R)-4·decyl_3_pyrrolidinyl]- 2-pyrazinamine; N-[(3R,4R)-4-(fluoromethyl)-3-°pyrrolidyl]_6-imidazo[1,2-a]pyridin-3-yl-2- Pyrazinamide; 6-imidazo[1,2-a]pyridin-3-yl-N-[(2S,3R)-2-indolyl-3-piperidyl]-2-pyrazinamine; 6- Imidazo[1,2-a]pyridin-3-yl-N-[(2R,3 S)-2-methyl-3-piperidinyl]-2-indolylamine; N-(3R)-3 Pyrrolidinyl-6-[7-(2,2,2-trifluoro-indolyloxy)imidazo[l,2-a]pyridin-3-yl]-2-pyrazinamine; 3 - [6_ [(3R)_, 3 "Chenylamino]] 2_ ° than thiol] _ 唾 并 [1,2 _a] Oryridin-7-ol; 6-mi 嗤 [l, 2-a]0 is more than -3-yl-N-[(2R,3R)_2-methyl_3·Bucking base]-2-pyrazine; 502 201130835 6-imidazo[1,2- a]pyridin-3-yl-N-[(2s,3S)-2_indolyl-3-piperidinyl]-2-α-proline 6-(6-gas mites and [i,2-a]0 is more than -3-yl)_n_[(3S,4S)-4-mercapto-3_ 吼 咬 ]]-2-nonylamine ; 6-imiphtho[l,2-a]n is more than indole-3-yl-N-[(3R,5R)_5-methyl-3-0 than each of the octyl]-2-decylamine; 6-[7·(3,3-Dimercaptobutoxy)imidazopyridine_3·yl]-N-(3R)-3_pyrylene-2·*1 than amine; 3-[1 -[(3R)_3·piperidinylamino]pyrazinyl]-isoxazo[丨,^]pyro-6-nonanol; 6·(7_ 曱oxy σ-mazole-[1,2_a] ° ratio biting) _n-[(3R,4R)-4_ phenyl^-吼 slightly biting base]-2-° ratio °qinamine; 503 1 _〇methylimidazo[1,2_a]pyridyl)_n -(3R)-3-piperidinyl decylamine, 6-[2_[(3-indolyl oxetanyl)methoxy]imidazo[^2·^ ° ratio bite &gt; 3-yl] -N-(3R)-3-Di:b fluorenyl-2-σϋπqinamine; 2 6-[7-[(3-indolyl-3-oxetanyl)methoxy]imidazo [丨, 2_a] 0 than -3-yl]-N-(3R)-3-a&gt;/^ dimethyl-2-aitn-heptylamine; 6-imidazo[l,2-a]pyridine-3- -N-[(3R,5R)-5-decyloxy-3-3-pyridyl]-2-pyrazinamine; &quot;6-imidazo[l,2-a]pyridin-3-yl-N -[(3R,5S)-S-(methoxyindolyl)-3-π比洛基基]Qin ; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,5S)-5-[(l.methylethoxy)methyl]-3-pyrrole) · pyrazinamide; 201130835 N-(6- ° m β sit and [1,2-a]π ratio β--3-yl-2-π thiol)-2·aza double bad [2.2.1 Hept-6-amine, 3-[6-[(lS,4R,6R)-2-azabicyclo[2.2.1]hept-6-ylamino]-2-pyridazinyl]-imidazo[ l,2-a]«Bistidine-7-carbonitrile; 6-(6-fluoroimidazo[l,2-a]»pyridin-3-yl)-N-[(2R,3S)-2- Mercapto-3-piperidinyl]-2-pyrazinamine; 6-(6-fluoroimidazo[l,2-a]acridin-3-yl)-N-[(2R,3R)-2- Mercapto-3-0 Chenbityl]-2-π-proline, 6-(6-fluoroimidazo[1,2-a]pyridin-3-yl)-N_[(2S,3R)- 2-mercapto-3-piperidinyl]-2-pyrazinamine; 3-[6-[(3R)-3-π比洛π定基基基]-2-π比嗓基]-p米σ And [1,2-a]pyridine-7-carbonitrile; 3-[6-[[(3R,4R)-4-methyl-3-indolyl]amino]-2-pyridazinyl ]-°m0 sit and [1,2-a]11 than bite-7-曱 guess, 3-[6-[[(3R,5S)-5-(曱oxyindolyl)-3-吼] Pyridyl]amino]-2-indole-0-yl]-. Rice 11 sits and [l,2-a]nttia -7-曱 guess, 3-[6-[[(3R,5R)-5-methyl-3-indolyl]amino]-2_ Pyridazinyl]-[sigma][1,2-Wang]0 is more than 唆-7-phthalonitrile; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3S,4R) -4-decyloxy-3-pyrrolidinyl]2-pyrazinamine-; 3_[6_[[(3R,4R)^4-mercapto-3-0-pyrrolidine]-amino]-2- π is more than 嗜-yl]- σ 唾 并 [1, 2-3] ° ratio bite -7-formamide; 6-imidazo[l,2-a] &quot; pyridine-3-yl-N- [(3R,5S)-5-(propoxyindolyl)-3-ntb^ octyl]-2-π-pyridylamine, 504 201130835 N-[(3R,5S)-5-(ethoxyl ))-3-°pyrrolidyl]-6-imidazo[1,2-&]1* is more than -3-yl-2-11 to 11-hhenylamine; 6-imidazo[1,2- a] pyridin-3-yl-N-[(3R,4R)-4-(l-methylethyl)-3-indenyl]-2-indolylamine; 6-imidazo[l, 2-a]pyridin-3-yl-N-[(3S,4R)-4-(2,2,2-trifluoroethoxy)-(3-pyrrolidinyl)-2-pyrazinamine; N- [(3R,4R)-4-ethyl_3_pyrrolidinyl]-6-imidazo[l,2-a]pyridin-3-yl-2-pyrazinamine; N-[(3R,4R) -4-cyclopropyl-3.pyrrolidinyl]-6-imidazo[l,2-a]pyridin-3-yl-2-π-p-amine; (3R,5R)_5-[(6- Imidazo[1,2- a]pyridin-3-yl-2-pyrazinyl)amino]-3-piperidinol; 6-imidazo[l,2-a]pyridine-3-yl-N-[(3R,4R)- 4-methyl-3-piperidinyl]-2-pyrazinamine; 6_(7_ chloroimidazo[1,2_a] «Bite·3_yl)-N-[(3R,4R)·4·methyl -3-派唆基]-2-° than decylamine; 6-(8-methylimidazo[1,2-a]acridin-3-yl)_N_(3R)_3_piperidinyl-24 ( ^Qinamine, 6-[7-(1曱-yl-1H-.biazole-4-yl)imidazo[na]pyridine_3_yl]-N-[(3R,4R)_4-mercapto-3" Ratio of 11 octylazines; &gt;H(3R,4RH-cyclopentyl_3_D-pyridyl)_6_(7-decyloxyimidazo[l,2-a]D is more than -3-yl) -2" than decylamine; N-[(3R, 4RM-cyclopropyl_3_鳞丝]_6·(7·methoxy oxime and [1,2-a] pyridine-3-ylation Amine; 505 201130835 6-味味[l,2-a] 吼-3-yl-3·methoxy_N_(3R)_3-pyrrolidinyl-2-pyrazinamine; 6 [7 曱 曱Ethoxy)ethoxy]π米嗤[i,2_a]u ratio π定_3_基]-N-(3R)-3-n ratio bite base_2-»»piazineamine; 6- Miso-[l,2_a]pyridin-3-yl-3-methyl-N-(3R)-3-pyrrolidinyl-2-pyrazinamine; 6-(6-chloroimidazo[i, ;2-a]pyridine_3j)_N_[(2S3R)_2_ 曱基_3_ Base]-2-° than decylamine; 6_(6_ chloroimidazo[l,2_a]pyridine_3_yl)_N-[(2r,3r)_2·indenyl·3_pyrazine]-2-amine ; N-[(2S,3R)-2-indolyl-3·tridinyl]·6-[6-(trifluoromethyl)imidazo[1,2-8]11 than -3-yl] -2-1»Biazinamide; N-[(2R,3R)-2-indolyl-3-piperidinyl]-6-[6-(trifluoromethyl)imidazo[l,2-a] Pyridin-3-yl]-2-pyrazinamine; 6-(6-chloro-sodium and [i,2-a]0 is more than -3-yl)-]Sf-[(3R,4R)-4- Methyl-3_pyridinyl]-2-pyrazinamine; ό-(6-chloroimithia[i,2-a]D is more than indole-3-yl)-Ν·(4,4-difluoro · 3-α bottom σ base)-2-11 than decylamine; N-(4,4-fluoro-3-cyclodentate)-6-[6-(trifluoromethyl) oxime [i , 2_a] 0 is more than -3-yl]-2-π than decylamine; α,α-monodecyl-3-[6-[(3R)-3-pyridine-based]-2-^ ratio Zinyl]-flavored s-[1,2-a]pyridine-6-methanol; 3-[6-[(3R)-3-piperidinylamino]-2-pyridazinyl]-imidazo[ Lia] bite-6-amine, 506 201130835 6-(7-fluoro miso[1,2-a]pyridyl)_N_(3R)_3_ π bottom bite_2_pyrazinamine; soil 6-(7 - Fluoroimidazo[1,2-Amphetidine_3_yl]&gt;^_[(3艮58)_5_(methoxymethyl)-3-° ratio slightly bite ]-2-oxazinamide; (2S,4R)_4-[(6-imidazo[1,2-a]acridinyl-3-yl-2-phenylazinyl)amino]-2-0 Biting methanol; N-[(3R,5S)-5-(methoxymethyl)_3_ oxaridinyl] winter (7-methyl oxazolo[l,2-a]pyridin-3-yl)- 2-pyrazinamine; N-[(3R,5S)-5-[(l-methylethoxy)methyl]_3_πpyrrolidyl]•印_methylimidazo[1,2-a] Pyridin-3-yl)-2-pyridazinamine; N [(3R,5S)-5-(ethoxymethyl)_3_^π each bite base]_6_(7_methyl 咪α sitting and [l, 2 -a]ntb«^-3-yl)-2-π-pyrazinamine; 6_(7-methoxyimidazo[Ha] „biidine_3_yl)-n-[(3r,5s)-5_[ (i_Methylethoxy)methyl]_3·吼洛基基]Biazinamide; n-[(3r,5s)-5-(ethoxymethyl) piroxime]_6(7· Methoxy rice 0 sits and [1,2-strong]° than bite-3-yl)-2-pyridazinamine; 6_(7_气咪) sits and [1,2 is more than bite _3· base) _N[(3R,5S)_5_(methoxymethyl)-3-σ ratio slightly biting base]_2-π than decylamine; (2S,4R)-4-[[6-(7-aerocarbazole) [12♦ than biting each of the pyridazine groups] Amino]-2-el: b biting methanol; v 6-(6-chloroimidazo[1,2_a]pyridine_3_yl)_N ^3R, 5S) 5_(decyloxymethyl)-3-oxazolidinyl]-2-n Bisylazine; 6-flavored saliva[l,2_a]n ratio bite_3_yl·5曱yl_N(10)3 brittle base_2_507 201130835 pyrazinamide; N_[(3R)-4,4-difluoro 3-piperidinyl]-6-imidazo[l,2-a]pyridin-3-yl-2-pyrazinamine; N-[(3S)-4,4-difluoro-3-pyridinyl -6-imidazo[l,2-a]acridin-3-yl-2-pyrazinamine; 6-imidazo[l,2-a]pyridin-3-yl-N-[(3S,5S -5-methoxy-3-piperidinyl]-2-° ratio β-Qinamine; 6-imidazo[1,2-a]pyridin-3-yl_N-[(3S,4S)-4 -Methoxy-3-piperidyl]-2-oxazinamine; 6-imidazo[1,2-a]pyridin-3-yl-N-[(3R,4R)-4-methoxy- 3-piperidinyl]-2-pyrazinium hydrochloride; 3-[6-[[(2R,3R)·2·indolylpiperidinyl]amino]_2·pyridazinyl]•imidazo[ 1,2-a]pyridine-7-phthalonitrile; 3-[6-[[(3R,4R)-4-cyclopropyl·3· ° piroxime]amino]-2-«»azine Imidazo[l,2-a]npyridin-6-indolecarbonitrile; 3-[6-[[(3R,4R)_4·cyclopropyl-3·&quot; 嘻 嘻]] ]_2_pyridinyl]-imidazo[l,2-a]&quot;bipyridyl-7-carbonitrile; (2S,3S)-N-[6-(7-methoxy methoxy-miso[i][i ,2-a]tr ratio σ定_3_基)_2-«bazinyl]·2_methyl-1-azabicyclo[2.2.2]oct-3- ; 6·(6-Fluoromazole-[l,2-a]pyridin-3-yl)-N-[(3R,5S)-5-(methoxymethyl)-3-° ratio Base]-2-n-pyrazinamine; 3-0 m° sit and [l,2_a]D«^-3-yl_5_[(3r)_3-tj than 嘻 胺 胺 ] ] ] 嗪 嗪 嗪Nitrile; N-(3S)-3-indolyl-6-[6-(trifluoromethyl)imidazolium (^, to] acridine 508 201130835 -3-yl]-2-pyrazinamine; -[[HH(3R)-3-indolyl ylamino]_2_ n than fluorenyl]imidazo[l,2_a]pyridine-7-yl]oxy]-ethanol; ((9) Winter-A (10)^ ^- such as each of the guanidinoamine pyridazinyl (tetrazolo[l,2_a]pyridine-7-yl]oxy]-1-propanol; (2S)-2-[[3-[H(3r) _3_piperidinylamino]_2_pyrazinyl]imidazo[l,2_a]0 is more than methoxy]-1-propanol; (2S)-l-[[3-[6-[( 3R)_3-ti bottom arylamino]·2_β is thiol] taste β sits and [l,2-a]° pyridine-7-yl]oxy]_2-propanol; (2R)-2- [[3-[6-[(3R)-3, pyridylamino]-2-pyrazinyl]imidazo[l,2_a]0 is more than _7_yl]oxy]-1·propanol ; 2-[[3 - [6-[(3R)-3 - arylamino]·2· η is 嗓 ]]]]米峻和[^,2_a] 〇比咬-7_基] ]-ethanol; 6-imidazo[l,2-a]pyridin-3-yl-5-mercapto-N-(3R)_3- (3R)-3-[[6-(6- 气咪和和[1,2♦比咬基)_2_吼azinyl]amino]-b-pyridinium Acid l,l-dimercaptoethyl ester; (3R)-3-[[6-(6-methoxy imi-β sitting and [i,2_a] σ is more than 唆3_yl)_2_ π than keel] 1,1-didecylethylamine of amino]-1-piperidinecarboxylate; (3R)-3-[[6-[7-(aminocarbonyl)imieno[10]exophylline]pyridazinyl] U-dimethyl ester of amino]-1_succinic acid; v (3R,4R)_4_ethoxy-3-[(6-味唾和[i,2外比咬3_基_2_ Phenylpyridinyl)amino]-1_piperidinecarboxylic acid phenylmethyl ester; (3R)-3-[(6+ sita[l,2-a] 吼3_yl~bazinyl)amine Base] small 509 201130835 1,1-dimethylethyl piperidinic acid; (3S)-3-[(6- oxazolo[i,2-ap-pyridyl_3_yl·&gt;bazinyl) (1,1-dimethylethylaminopiperidinic acid; (311)-3-[(6-_嗤[1,2-&amp;] bite_3_yl_2-fluorenyl) ) Amino group] is small. 1,1-dimethylethyl bromidecarboxylic acid; (3R,4R)-3_[(6-imidazo[1,2-a]acridin-3-yl-2-pyrazinyl)amino] · 4-mercapto-1-pyrrolidinecarboxylic acid lsl_didecylethyl ester; (3R)-3-[[6-[6-(trifluoromethyl) ortho-azolopyridinyl-3-yl]211比 嗪 ] 胺 胺 胺 胺 胺 丨 ^ ^ ^ ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (比 啶 -3- -3-yl]-2-pyrazinyl]amino]_4_methyl 丨 吡 pyrrolidine decanoic acid u dimethyl ethyl ester; '(3R)-3-[(6-imidazo[ Ha]pyridine_3_yl_3·methyl-2-pyrazinyl)amino]-1·piperidinecarboxylic acid 1,1-dimethylethyl ester; (3R)-3-[(5-cyano) 6_. rice saliva [1,2_a] bite _3_yl_2_pyridazinyl)amino]-1-piperidinic acid 1, _ dimethyl ester; dimethyl ethoxy) Alkyl]-3-bryridinyl]amino]-2-pyrazinyl]-imidazo[nypyridine-7-carboxylic acid methyl ester; (2S,4R)-2-(:fluoromethyl)_4_[( 6_ misxazo (10) pyridine _3_yl-2_pyrazinyl)amino]-1-pyrrolidine ruthenate 丨, 丨 dimethyl ester; (3R, 4S &gt; 4 · fluoro-Η ( 6. Dizozolyl [l,2-a]pyridin-3-yl-2-pyrazinyl)amino]-1-piperidinecarboxylic acid phenylmethyl ester; (3R 4R&gt;4-Fluoro-H(6.imidazo[Ua]pyridine-3-yl-2-phenylazinyl)amino]-1-piperidinecarboxylic acid phenylmethyl ester; 510 201130835 (3R, 4R)-3 -[(6-mimi-[1,2-a]σ is more than -3-yl-2-»-indenyl)amino]-4-methoxy-1-piperidinecarboxylic acid phenylmethyl ester; (2S,5R)-5-[(6-11 m β sita[1,2-a]11 is more than -3-yl-2-11-indenyl)amino]-2-methyl-1- Phenylmethyl piperidine; (211,5 ft)-5-[(6-° 嗤 嗤 [1,2-&amp;]° is more than -3-yl-2-11 than '1 yl) Amino]-2-methyl-l-pyrone phenylmethyl methacrylate; (3R)-3-[[6-[7-[2-(l-methylethoxy)ethoxy]imidazolium [^24] ° 咬-3-yl]-2-pyrazinyl]amino] slightly biting formic acid • dimethyl ethyl ester; and (3R)-3-[(6-imidazo[1,2_a ]0-pyridyl_3·yl_3_methoxy-2_n-pyridyl)amino]-1-pyrene 1,1-dimethylethyl ester 34. - a compound of formula (I) or a pharmaceutically acceptable salt or solvate or N-oxide or stereoisomer or deuterated derivative, R4 R„ Item defined in any one of items 24; and when the towel is a silk nitrogen atom, Ζ and as for the patent application number 1 x represents a -cr9 group, and the r8 succinyl group which is not bonded to 511 201130835 is bonded to the -zjchl- moiety, which is substituted with a substituent which is not a third butoxycarbonyl group or a benzyloxycarbonyl group. / 35. The compound of claim 34, wherein γ represents a -CR9 group and X represents a nitrogen atom. A pharmaceutical composition comprising a compound according to any one of claims 3 to 35, and a pharmaceutically acceptable diluent or carrier. 37. A combination product comprising: (丨) a compound according to any one of claims 33 to 35; and (丨丨) another compound selected from the group consisting of: a) - II Folate reductase inhibitors, such as Methotrexate or CH-1504; b) DH0DH inhibitors, such as leflunmide, teriflunomide or international patent application No. WO2008 Compounds described in No. 077639 and No. WO2009021696; c) Immunomodulators such as Glatiramer acetate (Copaxone), Laquinimod or 喧米喧莫Imiquimod; d) DNA synthesis and repair inhibitors, such as Mitoxantrone or Clad &amp;dribine; e) Anti-α4 integrin antibodies, such as Natalizumab (Natalizumab) Tysabri); f) α4 integrin antagonists such as r_1295, TBC_4746, 512 201130835 CDP_323, ELMD_002, Fimtegrast or TMC-2003; g) corticosteroids (c〇rtic〇id) and glucocorticoids (glucocorticoid)' Such as prednis〇ne or methylprednisolone, fluticas〇ne, mometascme or beta_metas〇ne; h) fumarate , such as u; 1) anti-TNFa antibodies, such as Infliximab, Adalimumab or Cert〇lizumab pegol; j) T/Valley I1 TNF α receptor , such as etanercept; k) anti-CD20 monoclonal antibodies, such as rituximab (Rituximab), $ gram C Gerelizumab, weimumab (__ secret) or TRU-015; Anti-CD52, such as alemtuzumab; m) anti-CD25 'such as daclizumab (dadizumab); η) anti-CD88 'such as ecuHzumab or pegilizumab (pexilizumab) ;) anti-IL12R/IL23R, such as ustekinumab. P) Calcineurin inhibition, such as cycl〇sporine A or tacrolimus ( Tacr〇iimus); q) IMPDH inhibitors, such as mycophenolate mophetyl; r) cannabis receptors , such as satex; 513 201130835 s ) chemokine CCRj pull μ μ antagonist, such as MLN-3897 or PS-031291; t) chemokine CCR2 antagonist, such as INCB_8696; u) NF- KB activation inhibitors, such as mln_〇4i5; v) SIP &amp; agonists, such as fmgolimod, BAF-312 or ACT128800; w) S1P dissociation enzyme inhibitors, such as; X) Syk inhibition Agents such as R_U2; y) PKC inhibitors, such as nvj&gt;_aeb〇71; z) M3 antagonists such as ti_pium or aclidinium; aa) long-acting beta-adrenergic motility An agonist, such as formoterol; bb) a vitamin D derivative, such as calcipotriol (calcip〇tri〇1) (^ Daivonex); cc) an acid-filled diacetate IV inhibitor , such as roflumilast or GRC-4039; dd) p38 inhibitor, such as ARRY 797; ee) MEK inhibitor, such as arry_i42886 or ARRY-438162; ff) ΡΙ3Κδγ inhibitor; ν gg) interferon Includes interferon pla, such as Avonex from Bi〇gen Idee, and Sinux from CinnaGen (Cin noVex) and Rebif from Merck Serono, and interferon p lb, 514 201130835 such as Betaferon from Schering and Betaseron from Berlex; and hh) interferon alpha, Such as Sumiferon MP; it is used simultaneously, separately or sequentially in the treatment of the human or animal body. 515